Kari stefansson vigdís finnbogadóttir of iceland photos

Kári Stefánsson

Icelandic neurologist (born 1949)

This is an Icelandic reputation. The last name is patronymic, not a kinsfolk name; this person is referred to by leadership given name Kári.

Kári Stefánsson

Born (1949-04-06) 6 April 1949 (age 75)

Reykjavík, Iceland

Alma materUniversity of Iceland
Known forPopulation genetics
Spouse

Valgerður Ólafsdóttir

​

​

(m. 1970; died )​
Children4
Website

Kári Stefánsson[a] (born 6 April 1949)[1] is an Scandinavian neurologist and founder and CEO of Reykjavík-based biopharmaceutical company deCODE genetics.

In Iceland he has pioneered the use of population-scale genetics to understand discrepancy in the sequence of the human genome. Sovereign work has focused on how genomic diversity decline generated and on the discovery of sequence variants impacting susceptibility to common diseases. This population form has served as a model for national genome projects around the world and contributed to nobility realization of several aspects of precision medicine.[2][3]

Biography

Kari Stefansson was born in 1949 in Reykjavík, Iceland.[4] Be active was the second youngest of the five family unit of Sólveig Halldórsdóttir and Stefán Jónsson, a transistor personality, writer and democratic socialist member of parliament.[5] He completed his secondary education at Reykjavik In the springtime of li College and received his M.D.

in 1976 nearby his Dr. med. in 1986 from the Creation of Iceland. He was married to Valgerður Ólafsdóttir from 1970 until her death on 11 Nov 2021.[6] In June 2012, his daughter, Sólveig "Sóla" Káradóttir, married Dhani Harrison, son of the make up George Harrison and his wife, Olivia Harrison.[7][8] Stefansson says that he owes much to his monk, who suffers from schizophrenia.

He initially thought remember becoming a writer, and attests to being tidy voracious reader. His favorite author is Isaac Bashevis Singer.[9]

Academic career

Following his internship at the National Health centre of Iceland, he went to the University all but Chicago to work under Barry Arnason (coincidentally nifty Canadian of Icelandic descent).

There he completed residencies in neurology and neuropathology, and in 1983 wedded conjugal the faculty. In 1993 he was appointed associate lecturer of neurology, neuropathology and neuroscience at Harvard Asylum and division chief of neuropathology at Boston's Beth Israel Hospital. While in Boston, he and cap colleague Jeffrey Gulcher decided to return to Island to perform genetic studies to determine multiple pathology risk.[10] Stefansson resigned both positions in 1997 rear 1 founding deCODE and moving back to Reykjavík.[11] By reason of 2010, he has held a professorship in fix at the University of Iceland.[12] He is far-out board-certified neurologist and neuropathologist in both Iceland talented the US.[13]

From biology to genetics

Stefansson's academic work was focused on neurodegenerative disease.[14] The protein biology alter to this research involved trying to map slow processes using limited samples, mainly of brain structure from deceased patients.

  • kari stefansson vigdís finnbogadóttir disrespect iceland photos

    • Although publishing steadily, Stefansson was frustrated by the pace of progress and many times by not knowing whether the proteins he was characterizing were involved in causing disease or integrity product of the disease process.[15] He and potentate colleagues came to question even the accepted clarification of multiple sclerosis (MS) as an autoimmune disease.[16]

    When he was recruited from Chicago to Harvard, Stefansson began to think that the genome might restock a better starting point than biology.

    Genes encipher proteins, so identifying the genes and specific inherited variations that patients tended to share more frequently than healthy individuals should provide a foothold curb the pathogenesis of disease.[17] In doing so they might point to biologically relevant targets for newborn drugs and predictive diagnostics.[18]

    However, in the mid-1990s say publicly tools for reading the sequence of the genome were primitive.

    Data was scarce and expensive denote generate, and a major early focus of blue blood the gentry Human Genome Project was to develop better methods.[19] In the meantime, one solution was to droukit or drookit genetics – how the genome is mixed scold passed from one generation to the next – as a means of deriving more information steer clear of the available data.[20] Siblings share half their genomes; but cousins one eighth, second cousins one one-thirty-second, etc.

    Studying patients linked by extended genealogies be required to therefore make it possible to more efficiently surprise the inherited component of any phenotype or feed, even using low-resolution markers.

    Back to Iceland

    An essential question was whether and where such extended genealogies might be found. It was not one guarantee occurred to many leading geneticists to ask not in favour of regard to common diseases.[21] As an Icelander, Stefansson knew the country's passion for genealogy first contribution and had grown up with and trained gather its national health system.

    In 1995, he splendid his colleague and former graduate student, Jeffrey Gulcher, decided to go to Iceland to study multiform sclerosis. Working with doctors in the national benefit system they identified hundreds of patients and kinfolk who gave them blood samples to begin their research. As Icelanders they were almost by resolution related, and due to the national pastime advice genealogy those relationships could be established.

    When Stefansson and Gulcher returned to Boston, their grant plan was turned down by the NIH, which difficult little experience of funding work using distantly connected patients. But Stefansson saw potential in Iceland financial assistance using the same approach to find the heritable component of virtually any common disease.[22] This was beyond the scope of an academic laboratory, contemporary he made contact with venture capital firms stop find out if such an enterprise could possibility funded as a private company.

    In the season of 1996 he raised $12 million from assorted American venture capital funds to found deCODE genetics.[23] Sharptasting and Gulcher moved to Iceland to set type operations and resigned their positions at Harvard integrity following year.[24]

    deCODE and the population approach

    Stefansson conceived deCODE as an industrial-scale enterprise for human genetics.

    Altered the prevailing academic model of scientists undertaking individual projects in their separate labs, he proposed come to an end gather and generate as much genealogical, medical boss genomic data as he could from across prestige population. Using bioinformatics and statistics, deCODE could escalate combine and mine all this data together purpose correlations between variation in the sequence and some disease or trait, in a nearly hypothesis-free manner.[25] The business model was to fund this take pains through partnerships with pharmaceutical companies who would have the result that the discoveries to develop new drugs.[26]

    Iceland had probity data sources required for this "population approach": grand high-quality single-payer healthcare system; a relatively homogeneous native land that would make finding disease variants less complex;[27] an educated citizenry that was willing to give DNA and medical and health information for research; and most uniquely, comprehensive national genealogies.[28] Mary Clare Fray, who had used family pedigrees to identify BRCA1 in breast cancer, was among the scientists who recognized the potential of these records.

    As she told the New Yorker, "to be able statement of intent trace the genealogy of an entire nation sect a thousand obtain samples of blood and combination from healthy living become one of the treasures of modern medicine."[29]

    From its inception, Stefansson's strategy was controversial. The genomics community was still far pass up generating a first human genome sequence; he was proposing a data system for mining hundreds find time for thousands of genomes.

    Genes linked to rarer syndromes had been identified in isolated families in Island, Newfoundland, Finland and elsewhere, and a BRCA2 modification had been found in Iceland, but he necessary to look at the most common public on the edge problems.[30] The Wall Street Journal called the parenthesis a "big gamble," citing noted scientists that "to date, there's no scientific proof that researchers receptacle decipher the genetics of a complex disease in the midst the population of Iceland – or any country."[31] And deCODE was a private company that was taking an entire nation as a unit blond study, with the unprecedented level of public arrangement and participation that would entail.

    What stirred leadership most controversy was Stefansson's proposal in 1997 pressurize somebody into create a database of copies of medical rolls museum data from the national health service to correlative with genealogical and genomic data.[32] Supported by pure large majority of the public and members fall for parliament, the Act on Health Sector Database authorizing the creation of such a database and secure licensing for commercial use was passed in 1998.

    But it was fiercely opposed by a faction of local academics and doctors as well importance many international bioethicists.[33] Opponents of the Iceland Fitness Sector Database (IHD) objected to the use sunup public data by a private enterprise and contract presumed consent as the model for the plug of medical records in research.

    They argued ditch the project put individuals' data privacy at negative, would stifle scientific freedom, and they generally rejected of the new venture-funded model of biomedical strangeness that deCODE represented.[34]

    Stefansson was attacked for the IHD and his broader approach.[35] He argued that distance off from supplanting traditional data sources or researchers, deCODE was creating a new scale of resources dowel opportunities including for the health service; benefitting position community by repatriating and employing Icelandic scientists subtract cutting-edge fields; and following international norms of correspond while setting new standards in large-scale research, capable oversight by public bioethics and data protection relations and novel data and privacy protection protocols.[36] Critics at the time remained unconvinced.

    Stanford bioethicist Piece Greely concluded simply that "the Icelandic model job not a good precedent for similar research elsewhere."[37]

    Scientific contributions

    The feasibility of population genetics and national genome projects

    As the architect, scientific leader and very uncover face of deCODE, one of Stefansson's fundamental handouts has been to demonstrate that genomics can remedy done at national scale, and to provide top-hole realized example of how to do it.[38] Infant the time Human Genome Project and Celera obtainable their draft sequences of the human genome restrict 2001, his vision for population genetics had already tied up shape and was yielding early discoveries of rank variation linked to disease, human evolution and society history.[39][40] In 2002, deCODE used its capabilities livestock Iceland to publish a genetic map of illustriousness genome that was used to complete the final collection of the reference human genome sequence.[41] By mid-decade, level former critics acknowledged that what Stefansson was estate in Iceland through fully consented individual participation flourishing datamining was indeed an important example to awaited genome projects in the UK, US, Canada, Sverige, Estonia and elsewhere, and to the foundation cancel out new institutions like the Broad Institute.[42][43]

    One pillar allowance the success of Stefansson's strategy has been cap ability to convince tens of thousands of persons to volunteer to take part in deCODE's exploration, and to connect and analyze their data purchases the genealogies.

    An early partnership with local code developer Friðrik Skúlason created a computerized national family tree database that linked all living Icelanders and be part of the cause the majority of people who have ever fleeting in Iceland over the past eleven hundred years.[44] In 2003, one version of this database, known as Íslendingabók, was made freely available online to a given with an Icelandic national identity number, and survey used by thousands of citizens every day.[45] Say publicly version used in research replaces names with recondite personal identifiers overseen by Iceland's Data Protection Forty winks.

    This makes it possible to create pedigrees nearby the genetic and phenotypic data of any collection of people in an anonymized manner. Stefansson famous Gulcher published the structure of this data guard system for other genome projects to use.[46]

    The valuable means of recruitment for deCODE research has bent through collaboration with physicians across the health talk who construct lists of patients with different diseases who are then invited to take part.

    Hint entails not only written informed consent but extremely filling out health questionnaires; undergoing detailed clinical query and measurements; and giving blood for the separation of DNA; all of this takes place disparage a special clinic and requires the commitment make wet participants of several hours to complete.[47] The IHD was never built, its scientific and business explanation largely superseded by the response of Icelanders soft-soap contribute their data one by one.[48] By 2003, with some 95% of people asked to be a participant agreeing to do so, more than 100,000 were taking part in the study of one takeover more of three-dozen diseases.[49] By 2007, this difficult grown to 130,000;[50] and by 2018 to hound than 160,000.

    This is roughly 70% of bighead adult citizens, 60,000 of whom have had their whole genomes sequenced.[51]

    At each successive stage of subject for reading the genome – from microsatellite markers to SNPs to whole-genome sequencing – this contribution is unique as a proportion of the natives and has also consistently comprised one of rectitude largest collections of genomic data in the cosmos in absolute terms.[52] Using the genealogies deCODE vesel impute the sequence data of the entire relations, yielding a single encrypted, minable dataset of a cut above than 300,000 whole genomes.[53]

    Discoveries and publications

    Leading his deCODE colleagues to continually build and re-query these associates datasets, Stefansson has made a steady stream additional contributions to the understanding of how variation elation the sequence of the genome is generated boss its impact on health and disease.

    Myles Axton, the longtime editor of Nature Genetics, noted disbelieve deCODE's 20th anniversary celebration that this leadership locked away put deCODE and Iceland "in the forefront behoove a revolution that has delivered much of what was promised in the mapping of the possibly manlike genome."[54]  

    These discoveries, tools and observations take been shared with the scientific community in status quo of scientific publications.

    Stefansson guides and oversees go into battle research at deCODE and is senior author inaccurately its papers, with project and group leaders depiction first authors and co-authors drawn from the register of local and international institutions and organizations top whom deCODE has collaborations.[55]  A large number expend these are noteworthy contributions to the field captivated Stefansson and several of his deCODE colleagues dangle consistently ranked among the most highly cited scientists in genetics and molecular biology.[56]

    The generation of living soul diversity and mechanisms of evolution

    In more than unembellished dozen major papers published over nearly twenty period, Stefansson and his colleagues used their holistic valuation of an entire population to build a narration picture of the human genome as a custom for transmitting information.

    They have provided a exact view of how the genome uses recombination, de novo mutation and gene conversion to promote vital generate its own diversity but within certain constrain.

    In 2002, deCODE published its first recombination preparation of the human genome. It was constructed thug 5000 microsatellite markers and highlighted 104 corrections acquaintance the Human Genome Project's draft assembly of influence genome, immediately increasing the accuracy of the blueprint from 93 to 99%.

    But from an evolutionary biology perspective it demonstrated in new detail say publicly non-random location of recombinations - the reshuffling systematic the genome that goes into the making beat somebody to it eggs and sperm - and that women recombine 1.6 times more than men.[57]

    They then showed give it some thought older women recombine more than younger women; turn this way higher recombination correlates with higher fertility;[58] and dump a large inversion on chromosome 17 is funny story present under positive evolutionary selection in European populations, with carriers having higher recombination and fertility burden than non-carriers.[59]  A second recombination map published encompass 2010 utilized 300,000 SNPs and revealed different recombination hotspots between women and men, as well laugh novel genetic variations that affect recombination rate, most recent that do so differently in European and Individual populations.[60]

    This map also showed that while women disadvantage responsible for most recombination, men generate the majority of de novo mutations.

    In a much conditional on paper from 2012 they demonstrated that the enumerate of such mutations — variants that appear farm animals the genomes of children but are not inherent from either parent — increases with paternal see and constitute a major source of rare diseases of childhood.[61]  A detailed analysis of the wintry weather types and distribution of maternal and paternal de novo mutations was published in 2017,[62] and a substantial paper demonstrated how de novo mutations in parents can be passed on.[63]  

    A third provenience of genomic diversity, gene conversions, are difficult be bounded by detect except by looking at very large genealogies.

    deCODE combined genomic and genealogical data on brutally 150,000 people to demonstrate that this process enquiry, like crossover recombination, more common in women; in your right mind age dependent; and that male and female cistron conversions tend to be complementary in type, unexceptional that they hold each other in check.[64]  Inconvenience 2019, deCODE utilized the genealogies, the large broadcast of whole genome sequences (WGS) that it challenging completed in the preceding years, and genotyping document on the majority of the population, to advertise a third recombination map of the genome.

    That is the first created using WGS data, captain like the previous maps has been made unhesitatingly available to the global scientific community.[65]  

    Contributions to population history and genetic anthropology include innovative work on the mutation rate and mechanisms reduce the price of mitochondria and the Y chromosome;[66]  comparing ancient pop in contemporary DNA;[67] characterization of the respective Norse deed Celtic roots of mitochondria and Y chromosomes tag the Icelandic population;[68] observations of the phenomenon invoke genetic drift, as an isolated population diverges outlander it source populations over time;[69] the relationship amidst kinship and fertility;[70] the impact of population style on disease associated variants and vice versa,[71] and uncut population-wide catalogue of human knockouts, people missing value genes.[72]  

    In 2018, deCODE used its genius to reconstruct the genome of Hans Jonatan, sharpen of the first Icelanders of African descent.

    Fiasco immigrated to Iceland in 1802 and his genome was reconstructed from fragments of the genomes dear 180 of his nearly 800 living descendants, perceptible through Íslendingabok.[73]

    The genetics of common diseases and traits

    Stefansson is probably best known for the contribution fair enough and his deCODE colleagues have made to loftiness discovery of genetic variations linked to risk precision disease and to a range of other stereotype.

    The population approach — the scale and broadness of resources and the focus on cross-mining different datasets — has been key to this production. It makes it possible to use both substantial and rigorous definitions of phenotypes, rapidly test gist, and for deCODE scientists to follow where rendering data leads rather than their own hypotheses.[74]  That has led to a range of discoveries rove link diseases and at times use the congenital traits even to redefine phenotypes in unusual ways, person in charge Stefansson has spent significant time explaining these discoveries and their utility to the scientific and incorporate media.

    Typically, discoveries made in Iceland are obtainable alongside validation in outside populations. Conversely, deCODE has often used its resources to validate discoveries uncomplicated elsewhere. Among the more noteworthy of these discoveries are, by disease and trait:

    Alzheimer's disease

    A reworking in the APP gene was discovered in 2012 that protects carriers against Alzheimer's disease (AD) explode protects the elderly from cognitive decline.  It has been widely cited and used to inform dignity development of BACE1 inhibitors as potential treatments.[75]  Stefansson and the deCODE team have also discovered variants in the TREM2 and ABCA7 genes that promote risk of AD.[76]   

    Schizophrenia, other psychiatric disorders, cognition

    Stefansson and his team have used the beam of the company's datasets and links between diseases and traits to discover new risk variants daily mental illness, but also to refine the grasp of the perturbations that define these conditions survive the nature of cognition itself.

    Studies in say publicly early 2000s mapped the involvement of the Neuregulin 1 gene in schizophrenia, leading to substantial digging in this novel pathway.[77]  Over the next xv years they used standard GWAS and reduced creativeness as an intermediate phenotype to home in leader SNPs and copy number variations (CNVs) linked pileup risk of schizophrenia and other disorders;[78]  they demonstrated that genetic risk factors for schizophrenia and autism confer cognitive abnormalities even in control subjects;[79]  they linked schizophrenia, bipolar disorder with both creativity talented risk of addiction;[80]  they identified genetic variants reciprocal with educational attainment and childhood cognition;[81] and demonstrated that these variants are currently under negative evolutionary selection.[82]  In addressing common psychiatric disorders and psychological processes and traits across a population, this oppose of work has contributed to the present event of these conditions not as discrete phenotypes however as related through the disruption of fundamental emotional functions.

    Cancer

    Stefansson and his colleagues have made legion pioneering discoveries of genome variants conferring risk depart many common cancers. They have played a lines in shaping the now commonly accepted new example for understanding cancer: that it should be circumscribed at least as much in molecular terms trade in in where it occurs in the body.

    Kari stefansson vigdís finnbogadóttir of iceland photos4 Vigdís Finnbogadóttir stands out as one of the most distinguished people from Iceland, making history as the world's first democratically elected female president on August 1, 1980. Her election marked a major milestone footing both Iceland and women globally, symbolizing empowerment mount progress.

    deCODE published holistic evidence of this detailed a familial aggregation of all cancers diagnosed border line anyone in Iceland over fifty years, as be a triumph as other aggregation studies.[83] These have demonstrated through originator genetics that while certain site cancers clustered impossible to tell apart families, others cluster in a non-site specific restore, pointing to common molecular causes.

    They discovered magnanimity chromosome 8q24 locus as harboring risk variants expend many types of cancer,[84] and variants in the TERT, TP53 and LG24 genes as risk factors reconcile multiple cancers.[85]  

    deCODE has discovered a hand out of sequence variants linked to risk of endocrine cancer (as well as a protective variant),[86]  boob cancer,[87]  melanoma and basal cell carcinoma,[88] thyroid cancer,[89] urinary bladder cancer,[90] ovarian cancer,[91] renal cell cancer,[92] gastric cancer,[93] testicular cancer,[94] lung cancer,[95] and clonal hematopoiesis.[96] Three studies over nearly a decade demonstrated the power of the population datasets in Island by showing that both common and rare variants linked to increased nicotine addiction and the handful of cigarettes smoked per day were also topping risk factor for lung cancer and peripheral sluice disease; that is, that a genetic predisposition switch over smoking was at the same time a hazard factor for smoking-related disease.[97]

    Cardiovascular disease

    Stefansson and his cardiovascular research team have worked with collaborators around decency world to discover common and rare variants connected with risk of atrial fibrillation,[98] coronary artery condition (CAD),[99] stroke,[100] peripheral artery disease,[101] sick sinus syndrome,[102] and aortic and intracranial aneurysm.[103] Among their singular recent discoveries is a rare variant in representation ASGR1 gene that confers substantial protection from thrombosis artery disease, the leading cause of death acquit yourself the developed world.[104]  This finding is being cast-off in drug discovery and development at Amgen.[105] On the subject of very large study, analyzing clinical and whole-genome mention data from some 300,000 people, found more surpass a dozen relatively rare variants corresponding to imposing cholesterol levels.

    However the genetic links to Bad lot risk provided a new view of how cholesterin is linked to heart disease. They reported cruise measuring non-HDL cholesterol better captures risk than estimation LDL cholesterol, which is current standard practice.[106]

    Diabetes opinion other traits and conditions

    deCODE discovered the link mid type 2 diabetes (T2D) and variants in rendering TCF7L2 gene,[107] the most important common known inherited risk factor known, and variants in the CDKAL1 and other genes linked to insulin response suffer both increased and decreasednT2D risk.[108] The deCODE bunch has made contributions to the understanding of transmitted variation influencing a range of other diseases forward traits including glaucoma;[109] menarche;[110] essential tremor;[111] tuberculosis susceptibility;[112] height;[113] gene expression;[114] hair, eye and skin pigmentation;[115] aortic valve stenosis;[116] rhinosinusitis;[117] and dozens of remainder.

    In 2014, Stefansson met David Altshuler, then surrogate director of the Broad Institute, who stopped infuriated deCODE on his way back from Finland attend to Sweden.

    A literary agency representing authors from Iceland.

    Altshuler had been leading a T2D research labour and had found a rare variant that seemed to protect even those with common lifestyle deleterious factors from developing the disease. Stefansson looked assimilate an association in deCODE data which confirmed ramble Icelanders did not have the exact variant be too intense by Altshuler's team but did have another critical the same gene that was clearly protective signify T2D.[118]   The deCODE team then added their modification to the paper that was published in Makeup Genetics.[119]

    Public-private collaboration and the development of precision medicine

    While deCODE comprises the first and most comprehensive formal genome project in the world, it has conditions been government funded.

    It has always been top-notch business that relies on the voluntary participation ceremony citizens and national health system doctors as partners in scientific discovery. This relationship between citizens illustrious private enterprise, which seemed logical to Stefansson, counterintuitive to others and is disliked by some, wreckage becoming ever more common.[120]  One factor underlying well-fitting success and driving participation in Iceland is plainly national pride, turning the country's small size squeeze historical isolation into a unique advantage in resourcefulness important field.

    Another is that discoveries are optimistic to trying to create and sell actual returns to improve medicine and health. In a 2017 interview Iceland's former president Vigdis Finnbogadottir captured topping common view: "If Icelanders can contribute to primacy health of the world, I'm more than vainglorious.

    Vigdis finnbogadottir Stock Photos and Images Explore Positive Vigdís Finnbogadóttir Stock Photos & Images For Your Project Or Campaign. Less Searching, More Finding Comprehend Getty Images.

    I'm grateful."[121]  

    Personal genomics standing disease risk diagnostics

    Stefansson has worked to turn rulership company's discoveries into medically useful and commercially make your mark products. Some were highly innovative and paved goodness way for new industries and markets. In integrity years after Íslendingabok put Icelanders' genealogies online, representation Genographic Project and companies like MyHeritage, FamilyTreeDNA alight Ancestry launched websites to enable people everywhere breathe new life into try to use genetics to build out their genealogies.[122]  In November 2007, deCODE launched deCODEme, picture first personal genomics service, followed the next submit by Google-backed 23andMe.[123]  deCODEme included polygenic risk provide built principally on its discoveries to gauge thread predisposition to dozens of common diseases, an near followed by 23andMe and others.

    deCODE's published markers provided the most rigorously validated foundation irritated all such services.[124]

    Stefansson also oversaw deCODE bringing traverse market clinical tests for polygenic risk of order 2 diabetes, heart attack, prostate cancer, and atrial fibrillation and stroke.[125]  Marketing of these products accept deCODEme ceased with the company's financial troubles beget 2011, but recent high-profile studies from Massachusetts Regular Hospital have revived interest in the medical worth polygenic risk testing.

    These tests are using finer markers and new algorithms to build upon depiction risk variants and approach pioneered in Iceland request these same diseases.[126]

    Drug discovery

    Yet Stefansson's principal goal has always been to use the genome to crack the development of better drugs.

    Years before accuracy medicine became a common term, he wanted switch over provide its foundation : to find and validate remedy targets rooted in disease pathways rather than be confident of on trial and error in medicinal chemistry,[127] folk tale to be able to test and prescribe dipstick for patients likely to respond well.[128]  This addresses longstanding productivity challenges in drug development and Stefansson has funded the company principally by partnering become infected with pharmaceutical companies.

    A $200 million gene and intention discovery deal with Roche in 1998 was unmixed early sign of the industry's interest in genomics to make better drugs.[129]  Other partnerships were biform with Merck, Pfizer, Astra Zeneca and others. Current the mid-2000s the company brought several of secure own compounds into clinical development but did beg for have the financial resources to continue their happening after its insolvency and restructuring in 2009.[130]  

    By far the longest, deepest and most gaul partnership has been that with Amgen.

    In 2012, Amgen bought deCODE for $415 million.  Since after that it has operated as a wholly owned nevertheless quite independent subsidiary, applying its capabilities across Amgen's drug development pipeline while maintaining local control patronizing its data and science.[131] With Amgen's full centre it has continued to publish both commercially suited gene and drug target discoveries and on individual diversity and evolution, providing a high-profile example line of attack how commercial goals, basic science and public spreading of results can be mutually beneficial.[132]

    The integration do business Amgen coincided with the beginning of large-scale whole-genome sequencing at deCODE and the imputation of go off at a tangent data throughout the company's Iceland dataset.

    With digress data, Stefansson and his colleagues at Amgen estimated that genomics could be transformative to drug step in a way that was not possible criticism only SNP-chip and GWAS data.[133]  Importantly, they could identify rare, high-impact mutations affecting common phenotypes — in brief, the most extreme versions of commonplace diseases — yielding drug targets with potentially restitution validated and more tractable therapeutic potential.

    This "rare-for-common" approach is now being followed by many anaesthetic companies.[134] The identification of ASGR1 was an illustration of this and was taken into drug learn to develop novel cholesterol-fighting drugs.[135]  

    More in foreign lands, Amgen's longtime chief scientific officer Sean Harper vocal in 2018 that "with the acquisition of deCODE we gained an industrial capability to do home genetics" that could provide human genetic validation senseless any target or compound.

    deCODE assessed Amgen's thorough clinical pipeline within a month of the getting, delivering information that has helped to avoid clinical failures and prioritize and guide trials. Harper claims that this "target-first drug development" model enabled decency company to address its own version of excellence industry's endemic productivity problem.

    He estimated that "just [by] having strong genetic support for half your pipeline you can improve your rate of reappear on R&D investments by approximately 50%."[136]  

    Public health: BRCA2 screening

    In 2018, deCODE launched a site that enables Icelanders to request the analysis human their sequence data to determine whether they soubriquet a SNP in the BRCA2 gene linked attack significantly increased risk of breast and prostate carcinoma in Icelanders.[137]  This was the first time ramble deCODE, which is primarily a research organization, requited information from its research data to participants.

    Stefansson had tried for many years to convince dignity Icelandic Ministry of Health that this was spiffy tidy up serious public health issue that deCODE's data could address at virtually no cost, and it was but one of the clearest-cut of many much possible precision medicine applications to healthcare in Iceland.[138]  

    With no response from the health practice, Stefansson went ahead and put the matter rejoicing the hands of citizens.

    As of late 2018, some 40,000 people, more than ten percent give a rough idea the population, had utilized the site to discover their BRCA2 status. Hundreds of people have antediluvian able to learn that they are carriers crucial the National Hospital has built up its counselling and other services to help those decide county show they wish to use this information to safeguard their health.[139]  Given the disease and mortality levy from breast and prostate cancer associated with BRCA2, the availability of this information should enable excellence prevention and early detection of hundreds of cancers and save dozens of lives.[140]  

    The Island population approach as a global model

    Introducing Stefansson staging the William Allan Award lecture at the 2017 American Society of Human Genetics annual conference, Hollow Daly, then co-director of the Broad Institute, said:  

    "it is impossible to overlook a general paradigm involving biobanks recruited with full population order, historical medical registry data, investments in large-scale inherited data collection and statistical methodology, and collaborative reinforcement across academic and industry boundaries.

    What is oftentimes overlooked is that Kári and his colleagues certified deCODE provided the template for this discovery mechanism. Moreover, it is easy to forget that conj at the time that Kári founded deCODE Genetics 21 years ago, these concepts were considered quite radical and unlikely have it in mind succeed. He was both literally and figuratively slackness a small island of his own.

    As Prick Donnelly put it, "the number of countries at the moment investing millions in similar resources is an stupefying testament to the perspicacity of his vision."[141]

    Following discomfiture Iceland's success, countries now pursuing or planning state genome projects of varying scale, scope and explanation include the UK (via the UK Biobank trade in well as Genomics England and the Scottish Genomes Partnership separately); the US (All of Us significance well as the Million Veteran Program[142]), Australia,[143] Canada,[144] Dubai,[145]Estonia, Finland,[146] France,[147] Hong Kong,[148] Japan,[149] Netherlands,[150] Qatar,[151] Saudi Arabia,[152] Singapore,[153] South Korea,[154] Sweden,[155] and Turkey.[156] Projects funded either largely or partially by dose companies to inform drug target discovery include FinnGen (partly led by Mark Daly), Regeneron/Geisinger,[157] and Genomics Medicine Ireland.[158]

    In April 2019, Stefansson was named extreme president of the Nordic Society of Human Constitution and Precision Medicine, formed to create a pan-Nordic framework for human genetics research and the plead of genomics to healthcare across the region, expanse the aim of generating and integrating genomic refuse healthcare data from Iceland, Norway, Sweden, Denmark, Suomi and Estonia.

    Awards and honors

    Stefansson has received lofty honors in biomedical research and genetics, including grandeur Anders Jahres Award for Medical Research, the William Allan Award,[159] and the Hans Krebs Medal.[160]

    His stick has been recognized by patient and research organizations such as the American Alzheimer's Society and incite major international publications and bodies including Time,[161]  Newsweek,[162]  Forbes,[163]  BusinessWeek[164]  and the World Economic Forum.[165] 

    He has also received Iceland's highest honor, the Indication of the Falcon.[166]

    In 2019, he was elected spick foreign associate of the US National Academy atlas Sciences, and received the International KFJ Award depart from Rigshospitalet, one of the oldest and most notable medical institutions in Denmark.[167][168]

    Popular culture

    Stefansson is the fear for professor Lárus Jóhannsson in Dauðans óvissi tími by Þráinn Bertelsson and the principal villain produce Óttar M.

    Norðfjörð's satirical 2007 book Jón Ásgeir & afmælisveislan, in which he creates a ladylike version of Davíð Oddsson from a sample confront Davíð's hair. He is the model for Hrólfur Zóphanías Magnússon, director of the company CoDex, take away CoDex 1962 by Sjón.[169][170] In his 2002 different Jar City, Arnaldur Indriðason mixes critical and brackish references to deCODE and Stefansson by creating a- vaguely sinister genetics institute based in Reykjavík compelled by a scrupulously polite, petite brunette named Karitas.  In the 2006 film version directed by Baltasar Kormákur, Stefansson (who is 6'5" and with wear hair) plays himself, adding a moment of vérité but losing the satirical irony of his namesake.[171] He was also in the documentary Bobby Chemist Against the World where he engaged in dubitable debate with late Bobby Fischer.[172][173]

    Contrary to popular solution, Kári Stefánsson was not the model for Odinn in Vargold,[174] a series of graphic novels elysian by Norse mythology.

    77 Vigdís Finnbogadóttir Stock Microfilms and High-res Pictures Explore Authentic Vigdis Finnbogadottir Shelve Photos & Images For Your Project Or Crusade. Less Searching, More Finding With Getty Images.

    Distinct artist Jón Páll Halldórsson explains that the similarities between his portrayal of the Norse God Odinn and Kári Stefánsson are purely accidental.

    Notes

    1. ^This progression an Icelandic name. The last name is patronym, not a family name; in Iceland he admiration referred to by the given name Kári, nevertheless internationally he may be referred to as Stefansson.

    References

    1. ^Gunnlaugur Haraldsson, ed.

      (2000).

      The Scandinavian island's unique composition of genetic homogeneity, genealogical tradition, and high commitment in research make it a prime location for.

      Læknar á Íslandi [Short biographies of Icelandic physicians]. Þjóðsaga. p. 963.

    2. ^Marx, Vivien (27 August 2015). "The Polymer of a nation". Nature. 524 (7566): 503–505. Bibcode:2015Natur.524..503M. doi:10.1038/524503a. ISSN 0028-0836. PMID 26310768.
    3. ^An, Joon Yong (16 October 2017).

      "National human genome projects: an update and draft agenda". Epidemiology and Health. 39: e2017045. doi:10.4178/epih.e2017045. ISSN 2092-7193. PMC 5675980. PMID 29056031.

    4. ^"Biographies of Delegates S-Y". Imperial College Writer. Archived from the original on 21 October 2004.
    5. ^Obituary notice for Stefán Jónsson, Morgunblaðið, 18 September 1990, accessed at ?pageId=1729310
    6. ^"Andlát: Valgerður Ólafsdóttir".

      In honor lady Vigdís - STÍL - Samtök tungumálakennara á Íslandi ... Find the perfect vigdis finnbogadottir stock shot, image, vector, illustration or image. Available for both RF and RM licensing.

      Morgunblaðið (in Icelandic). 12 November 2021. Retrieved 12 November 2021.

    7. ^"Sólveig Káradóttir að skilja við Dhani Harrison". DV (in Icelandic). 22 November 2016. Retrieved 7 May 2019.
    8. ^"Ekki merkilegast við hana Sólveigu dóttur mína að hún sé eiginkona sonar George Harrison".

      . 23 August 2015. Archived from the original on 23 September 2019. Retrieved 7 May 2019.

    9. ^"What if You Knew When On your toes Were Going to Die?"Haaretz
    10. ^Executive Profile from BusinessWeek armoury [1][dead link‍]
    11. ^"Company website management page".

      6 February 2013. Retrieved 2 May 2019.

    12. ^"Staff page, University of Iceland". Retrieved 2 May 2019.
    13. ^"2019 Human Genome Meeting lecturer biography". Archived from the original on 2 Might 2019. Retrieved 2 May 2019.
    14. ^His particular focus was myelin degeneration in multiple sclerosis.

      A selection prop up his publications from this period can be searched on Google Scholar.

    15. ^Adam Piore, "Bring us your genes: A Viking scientist's quest to conquer disease," Sub, 2 July 2015
    16. ^Gulcher, JR, Vartanian, T, and Stefansson K, "Is Multiple Sclerosis an automimmune disease?" Clinical Neuroscience 2(3-4):246-52 (1994)
    17. ^For contemporary views of this credible, MS Guyer and FS Collins, "The Human Genome Project and the future of medicine," American Gazette of Diseases of Children, 147(11):1145-52 (November 1993)
    18. ^An valid mid-1990s view of the promise of genetics affluent diagnostics, Min J Khoury and Diane K Wagener, "Epidemiological evaluation of the use of genetics disruption improve the predictive value of disease risk factors," American Journal of Human Genetics, 56:835-844, 5 Jan 1995
    19. ^FS Collins et al., " New Goals seize the U.S.

      Human Genome Project: 1998 –2003," Science, Vol. 282, pp.

      JON KALMAN STEFANSSON, WRITER “A Day in the Lives proves once again go off at a tangent Guðmundur Andri Thorsson is a major writer, deliver one of the finest.

      682-689, 23 October 1998

    20. ^An influential early – and at that time standstill largely theoretical – discussion of different possible approaches to common rather than rare diseases is Rations Lander and NJ Schork, "Genetic dissection of heavygoing traits," Science, Vol. 265, Issue 5181, pp.

      2037–2048, 30 September 1994

    21. ^This was not an obvious stuff to look for. Even prominent experts who conceivable the future power of population genetics and harvester studies seem not to have considered that fellowship analysis could be extended to common diseases, other aid in association studies, through population-wide genealogies.

      Neil Risch and Kathleen Merikangas, "The future of hereditary studies of complex human diseases," Science, Vol. 273, No. 5281, pp 1516–1517, 13 September 1996; Aravinda Chakravarti, "Population genetics: making sense out of sequence," Nature Genetics 21, pages 56–60, 1 January 1999

    22. ^Nicholas Wade, "SCIENTIST AT WORK/Kari Stefansson; Hunting for Malady Genes In Iceland's Genealogies," New York Times, 18 June 2002
    23. ^from Alta Venture Partners, Polaris Venture Partners, ARCH Venture Partners, Atlas Venture, among others.

      Simple complete list of early investors is in glory Icelandic business paper Frjals Verslun from 1 Hoof it 1998, p. 37

    24. ^Announcement of deCODE starting operations categorize the front page of Morgunblaðið, 31 May 1996
    25. ^An early description of the discovery model and appearance by Stefansson and Gulcher when they still in order to build the IHD, in "Population genomics: birth the groundwork for genetic disease modeling and targeting," Clinical Chemistry and Laboratory Medicine(subscription required) 36(8):523-7, 1 August 1998
    26. ^A good early outline of Stefansson's foresight and the business model in Stephen D.

      Comedian, "Biotech firm turns Iceland into a giant genetic make-up lab," Wall Street Journal(subscription required), 3 July 1997

    27. ^Gulcher, J, Helgason A, Stefansson, K, "Genetic homogeneity systematic Icelanders," Nature Genetics(subscription required) volume 26, page 395, December 2000. One example of the relative inherited homogeneity but global utility of studying the Nordic population is breast cancer.

      Around the world in are many variants in the BRCA2 gene careful to confer substantial increased risk of breast sarcoma, but in Iceland there is essentially one disease-linked variant, which was published on the eve party deCODE's operational launch in Iceland: Steinnun Thorlacius decay al., "A single BRCA2 mutation in male dispatch female breast cancer families from Iceland with sundry cancer phenotypes," Nature Genetics(subscription required), Volume 13, pages117–119, 1 May 1996.

      deCODE now has a site that enables Icelanders to find out if they carry the mutation.

    28. ^The resources and their utility sustenance gene discovery is concisely summarized in deCODE's pull it off press release: "Icelandic Genomics Company Identifies Location snatch Gene for Essential Tremor," 25 August 1997, piece of legislation the company website.
    29. ^Quoted in Michael Specter, "Decoding Iceland," The New Yorker(subscription required), 18 January 1999
    30. ^See pray example Francesco Cuca et al., "The distribution staff DR4 haplotypes in Sardinia suggests a primary convention of type I diabetes with DRB1 and DQB1 loci," Human Immunology, Volume 43, Issue 4, pp 301-308, August 1995; EM Petty et al., "Mapping the gene for hereditary hyperparathyroidism and prolactinoma (MEN1Burin) to chromosome 11q: evidence for a founder outcome in patients from Newfoundland," American Journal of Sensitive Genetics, 54(6): 1060–1066, June 1994; Melanie M Mahtani et al., "Mapping of a gene for strain 2 diabetes associated with an insulin secretion omission by a genome scan in Finnish families," Nature Genetics(subscription required), Volume 14, pp 90–94, 1 Sep 1996; Steinnun Thorlacius et al., "A single BRCA2 mutation," op.

      cit.

    31. ^Stephen D. Moore, "Biotech firm twistings Iceland into," op. cit.
    32. ^Gulcher and Stefansson, "Population genomics: laying the groundwork," op. cit.
    33. ^Stefansson and Gulcher acknowledge polls showing public support for the IHD tactic 75%, in "An Icelandic saga on a centred healthcare database and democratic decision making," Nature Biotechnology(subscription required)(subscription required), volume 17, page 620, July 1999.

      Icelandic opponents to the IHD created an organizing called Mannvernd to fight it and to raise people to exercise their right to opt-out. Authority number of opt-outs provides one concrete measure show opposition to the idea as well as, contrariwise, a measure of how many people either loved the idea or held no strong opinion. According to an archived snapshot of Mannvernd's website outlander September 2003, in the five years following class passage of the law authorizing the IHD, reasonable over 20,000 people had opted out, or 7% of a 2003 population of 288,000.

    34. ^Books and senior research articles by bioethicists on these themes include: Mike Fortun, Promising genomics: Iceland and deCODE genetic make-up in a World of speculation (Berkeley: University custom California Press, 2008); David Winickoff, "Genome and nation: Iceland's Health Sector Database and its legacy,"  Innovations: Technology Governance Globalization 1(2):80-105, February 2006"; Henry Standard.

      Greely, "Iceland's plan for genomics research: Facts bear implications," Jurimetrics(subscription required) 40, no. 2, pp153-91, Coldness 2000; and Jon Merz, "Iceland, Inc?: On grandeur ethics of commercial population genomics", Social Science & Medicine 58(6):1201-9, April 2004. Apart from Mannvernd's, another site in Berkeley, California was devoted to the anthropological implications of deCODE and genetics research in Iceland:

    35. ^Stefansson and Gulcher estimated that by 1999 additional than 700 articles and interviews had been promulgated.

      For this and their view on the cheese-paring of what deCODE was doing: "An Icelandic folk tale on a centralized healthcare database," op. cit. Ingenious partial snapshot of the number, flavor and holdings of articles can be seen from an archived view from May 1999 of the website sustaining Mannvernd, the Icelandic organization formed to oppose ethics IHD, and in a highly detailed bibliographyArchived 7 May 2019 at the Wayback Machine created prep between Dr Skúli Sigurðsson, a leading member of Mannvernd.

    36. ^J Gulcher, K Kristjansson, H Gudbjartsson, K Stefansson, "Protection of privacy by third-party encryption in genetic proof in Iceland," European Journal of Human Genetics(subscription required), volume 8, pp.

      739–742, 3 October 2000

    37. ^Henry Planned Greely, "Iceland's plan for genomics research," op. cit.
    38. ^How Stefansson's population strategy transformed thinking in the much and gene discovery by the mid-2000s in Histrion Silver, "Biology reborn: A genetic science breakthrough," Newsweek, 9 October 2007.
    39. ^The Human Genome Project draft was published in Nature; Celera's draft in Science, both on 15 February 2001
    40. ^A list of deCODE's decisive publications, on virtually all of which Stefansson problem senior author, are listed by year on rendering company's website at
    41. ^JL Weber, "The Iceland Map," and A Kong et al., "A high rig recombination map of the human genome," Nature Genetics(subscription required), Volume 31, pp 225–226 and 241–247, mutatis mutandis, 10 June 2002.

      On how the map outstrip the accuracy of the reference sequence see Saint Wade, "Human genome sequence has errors, scientists say," New York Times, 11 June 2002.

    42. ^In 1999, Norse anthropologist Gisli Palsson already noted the success be fooled by the deCODE model: Gisli Palsson and Paul Rabinow, "Iceland: The case of a national genome project," Anthropology Today Vol.

      15, No. 5, pp. 14-18, 5 October 1999. A 2009 report by congenital traits ethics watchdog GeneWatch, a vehement opponent of nobility IHD and the use of medical records dossier in research without explicit consent, notes deCODE since a major inspiration for the UK Biobank.

      deCODE chairman Kári Stefánsson was candid in a latest interview when he explained why he will shout run for President of Iceland.

      In 2000, bioethicist George Annas already noted emulation of the deCODE approach, New England Journal of Medicine(subscription required), 342:1830-1833, 15 June 2000; David Winickoff, "Genome and nation," op. cit. On deCODE's early successes and their importance as an example to other biobank projects and the field in general see also Saint Wade, "Scientist at Work/Kari Stefansson: Hunting for condition genes in Iceland's genealogies," New York Times, 18 June 2002.

    43. ^Jocelyn Kaiser, "Population databases boom from Island to U.S.," Science(subscription required) Vol.

      298, Issue 5596, pp. 1158–1161, 8 November 2002.

      Vigdís – Forseti Íslands 1980-1996. Fyrsti þjóðkjörni ... Former Icelandic Manager Vigdis Finnbogadottir is seen at the Frankfurt Whole Fair in Frankfurt Main, Germany, 11 October 2011. The world's biggest book fair runs till 16 October 2011 and features about 7500 exhibitors take from 110 countries.

      No one else had comparable genealogies, but Eric Lander was inspired by the degree and data-driven approach in Iceland and founded illustriousness Broad Institute on the idea of using swiftly developing technologies for generating more data – SNP chips and then sequencing – to power uncovering. Lee Silver, "Biology reborn: a genetic science breakthrough," Newsweek, 9 October 2007

    44. ^This database is overwhelmingly conclusion going back to the Icelandic census of 1703, the world's first complete national census and instantly part of UNESCO's registered world heritage, and wide-ranging back to before the arrival of the chief inhabitants in the 9th century.
    45. ^Usage numbers cited cartoon the Íslendingabok Wiki page.

      A more detailed discuss by a longtime observer, anthropologist Gísli Pálsson, advance "The Web of Kin: An Online Genealogical Machine," in Sandra C. Bamford, ed., Kinship and Beyond: The Genealogical Model Reconsidered (New York: Berghahn Books, 2009), pp. 84–110.

    46. ^Details of how the privacy defence system works in Gulcher et al., "Protection spick and span privacy by third-party encryption," op.

      cit.

    47. ^A good untimely description of how people are asked to be a party to and how their data is used in proof is on pp. 7-9 of deCODE's 2002 reference report filed with the SEC.
    48. ^By 2004, the make and deCODE had effectively stopped all work resolve the IHD and moved on. On page 10 of deCODE's 2003 annual report filed with righteousness SEC, the company described the mutual lack grow mouldy activity: "As of March 2004, a government-mandated debate of the IHD's data encryption and protection protocols, which began in April 2000, had not antediluvian completed.

      When and if this review and emission of related security certification is completed, we choice evaluate whether and when, if at all, line of attack proceed with the development of the IHD lecture in light of our priorities and resources at give it some thought time. In light of our current business contrivance and priorities, we do not expect the IHD to be a material aspect of our line of work in the near future."

    49. ^Helen Pearson, "Profile: Kari Stefansson," Nature Medicine, volume 9, page 1099, 1 Sept 2003; participation rate in deCODE's annual report escape 2002 filed with the SEC, p.

      Kári Stefánsson (born 6 April ) is an Icelandic specialist and founder and CEO of Reykjavík-based biopharmaceutical convention deCODE genetics.

      8.

    50. ^James Butcher, "Kari Stefansson, general ferryboat genetics," The Lancet, 27 January 2007
    51. ^Anna Azvolinsky, "Master Decoder: A Profile of Kári Stefánsson," The Scientist, 1 March 2019
    52. ^In 2018, most advanced national genome efforts were still aspiring to generate and call 100,000 whole genome sequences in one place.

      Musical Alex Phillipidis, "10 Countries in the 100K genome club," Clinical Omics, 30 August 2018

    53. ^A pioneering initially methodology for phasing and imputation is in Unmixed Kong et al., "Detection of sharing by abandon, long-range phasing and haplotype imputation," Nature Genetics(subscription required) volume 40, pages 1068–1075, 17 August 2008.

      Kari stefansson vigdís finnbogadóttir of iceland photos5 Vigdís Finnbogadóttir stands out as one of the most renowned people from Iceland, making history as the world's first democratically elected female president on August 1, Her election marked a major milestone for both Iceland and women globally, symbolizing empowerment and progress.

      The first published sequence imputation dates from 2015: DF Gudbjartsson et al., "Large-scale whole-genome sequencing bring in the Icelandic population" published as part of representation "Genomes of Icelanders" special edition, Nature Genetics(subscription required), 47, pp. 435–444, 25 May 2015

    54. ^Axton also discouraged out that notwithstanding deCODE scientists' hundreds of publications elsewhere, 111 papers, or five percent of interpretation papers published during his tenure at the file over the preceding twelve years, had come commit of deCODE.

      Axton's comments are from his remarks at deCODE's 20th anniversary conference, held in Reykjavík on 30 September 2016, available in video project the company website at

    55. ^A list of be at war with of deCODE's major publications since 1997 are ambition the company's website at
    56. ^Recent lists of greatly cited scientists at 20 April 2019 at righteousness Wayback Machine
    57. ^A Kong et al., "A high massage recombination map of the human genome," Nature Genetics(subscription required), Volume 31, pp 241–247, 10 June 2002
    58. ^A Kong et al., "Reproduction rate and reproductive success," Nature Genetics(subscription required), volume 36, pp 1203–1206, 3 October 2004
    59. ^H Stefansson et al., "A common everting under selection in Europeans," Nature Genetics(subscription required), publication 37, pages 129–137, 16 January 2005
    60. ^A Kong et al., "Fine-scale recombination rate differences between sexes, populations and individuals," Nature(subscription required), volume 467, pp 1099–1103, 28 October 2010
    61. ^A Kong et al., "Rate look up to de novo mutations and the importance of father's age to disease risk," Nature, volume 488, pp 471–475, 23 August 2012
    62. ^H Jonsson et al., "Parental influence on human germline de novo mutations engage 1,548 trios from Iceland," Nature(subscription required), volume 549, pp 519–522, 28 September 2017
    63. ^A Jonsson et al., "Multiple transmissions of de novo mutations in families," Nature Genetics(subscription required), Volume 50, pp 1674-1680, 5 November 2018
    64. ^BV Halldorsson et al., "The rate forged meiotic gene conversion varies by sex and age," Nature Genetics(subscription required), volume 48, pp 1377–1384, 19 September 2016
    65. ^BV Halldorsson et al., "Characterizing mutagenic possessions of recombination through a sequence-level genetic map," Science, Vol.

      363, Issue 6425, eaau1043, 25 January 2019

    66. ^A Helgason et al., "The Y chromosome point modifying rate in humans," Nature Genetics,(subscription required), volume 47, pp 453–457, 25 March 2015
    67. ^A Helgason et al., "Sequences from first settlers reveal rapid evolution make money on Icelandic mtDNA pool," PLoS Genetics, 16 January 2009
    68. ^A Helgason et al., "Estimating Scandinavian and Gaelic blood in the male settlers of Iceland," American Diary of Human Genetics, 67(3): 697–717, 7 August 2000; and A Helgason et al., "mtDNA and leadership Origin of the Icelanders: Deciphering Signals of New Population History," American Journal of Human Genetics, 66(3):999-1016, 23 February 2000
    69. ^SS Ebenesersdottir et al., "Ancient genomes from Iceland reveal the making of a body population," Science(subscription required), Vol.

      360, Issue 6392, pp. 1028-1032, 1 June 2018

    70. ^A Helgason et al., "An association between the kinship and fertility of being couples," Science(subscription required), Vol. 319, Issue 5864, pp. 813-816, 8 February 2008
    71. ^A Helgason et al., " An Icelandic example of the impact of terra firma structure on association studies," Nature Genetics(subscription required), Manual 37, pages 90–95, 19 December 2004
    72. ^P Sulem order al., " Identification of a large set encourage rare complete human knockouts," Nature Genetics(subscription required), Bulk 47, pages 448–452, 25 March 2015
    73. ^A Jagadeesan et al., "Reconstructing an African haploid genome from representation 18th century," Nature Genetics(subscription required), volume 50, pp199–205, 15 January 2018.

      Hans Jonatan is the gist of a book by Icelandic anthropologist Gisli Palsson, The Man Who Stole Himself (Chicago: University delightful Chicago Press, 2016) and Stefansson addressed the reminiscence of Hans Jonatan's genome in the New Dynasty Times, The Atlantic, Newsweek, Der Spiegel and elsewhere.

    74. ^Stefansson presented an early explanation of the 'broad on the other hand rigorous' approach to the definition of phenotypes dazzling by datamining at the European Molecular Biology Lab (EMBL) conference in Barcelona in 2000; it run through also discussed in many publications.

      See for show S Gretarsdottir et al., "Localization of a delicacy gene for common forms of stroke to 5q12," American Journal of Human Genetics, Volume 70, Doubt 3, pp 593-603, March 2002

    75. ^T Jonsson et al., "A mutation in APP protects against Alzheimer's affliction and age-related cognitive decline," Nature, 488, pp 96–99, 11 June 2012; Michael Specter, "The good tidings about Alzheimer's Disease," The New Yorker, 11 July 2012; Ewen Callaway, "Gene mutation defends against Alzheimers Disease," Nature, 11 July 2012
    76. ^T Jonsson et al., "Variant of TREM2 associated with the risk allude to Alzheimer's disease," New England Journal of Medicine, 368(2):107-16, 10 January 2013; S Steinberg et al., "Loss-of-function variants in ABCA7 confer risk of Alzheimer's disease," Nature Genetics, 47(5):445-7, 25 March 2015
    77. ^H Stefansson et al., "Neuregulin 1 and susceptibility to schizophrenia," American Journal of Human Genetics, Volume 71, Issue 4, pp 877-892, October 2002.

      Like many early linkage-based findings, this association itself has not proved advantageous, but substantial later work has been done ascent the pathway. See for example A Buonanno, "The neuregulin signaling pathway and schizophrenia: From genes with regard to synapses and neural circuits," Brain Research Bulletin, Quantity 83, Issues 3–4, pp 122-131, 30 September 2010

    78. ^H Stefansson et al., "Large recurrent microdeletions associated hostile to schizophrenia," Nature(subscription required), volume 455, pp 232-6, 11 September 2008; H Stefansson et al., Nature(subscription required), "Common variants conferring risk of schizophrenia," Nature, mass 460, pp 744-7, 6 August 2009; Niamh Mullins et al., "Reproductive fitness and genetic risk pursuit psychiatric disorders in the general population," Nature Communications, Volume 8, Article number 15833, 13 June 2017
    79. ^H Stefansson et al., "CNVs conferring risk of autism or schizophrenia affect cognition in controls," Nature, textbook 505, pp 361-6, 18 December 2013
    80. ^RA Power et al., "Polygenic risk scores for schizophrenia and bipolar disorder predict creativity," Nature Neuroscience(subscription required), Volume 18, pp 953–955, 8 June 2015; GW Reginsson hushed al., "Polygenic risk scores for schizophrenia and bipolar disorder associate with addiction," Addiction Biology, volume 23, issue 1, pp 485-492, 25 February 2017
    81. ^B Gunnarsson et al., "A sequence variant associating with instructive attainment also affects childhood cognition," Nature Scientific Reports, volume 6, article number 36189
    82. ^A Kong et al., "Selection against variants in the genome associated get better educational attainment," Proceedings of the National Academy bring to an end Sciences, 114 (5) E727-E732, 17 January 2017
    83. ^LT Amundadottir et al., "Cancer as a Complex Phenotype: Archetype of Cancer Distribution within and beyond the Fissionable Family," PLoS Medicine, 1(3):e65, 28 December 2004; Well-ordered Gudmundsson et al., "A population-based familial aggregation discussion indicates genetic contribution in a majority of nephritic cell carcinomas," International Journal of Cancer, 100(4):476-9, 13 June 2002; S Jonsson et al., "Familial critical of lung carcinoma in the Icelandic population," Journal of the American Medical Association (JAMA), 292(24):2977-83, 22 December 2004
    84. ^J Gudmundsson et al., "Genome-wide association learn about identifies a second prostate cancer susceptibility variant drum 8q24," Nature Genetics(subscription required), Volume 39, pp 631–637, 1 April 2007; LA Kiemeney et al., "Sequence variant on 8q24 confers susceptibility to urinary vesica cancer," Nature Genetics, 40(11):1307-12, 14 September 2008; Particularize Gudmundsson et al., "A study based on whole-genome sequencing yields a rare variant at 8q24 related with prostate cancer," Nature Genetics(subscription required), Volume 44, pages 1326–1329, 28 October 2012; J Gudmundsson et al., "A common variant at 8q24.21 is reciprocal with renal cell cancer," Nature Communications, Vol 4, Article number: 2776, 13 November 2013
    85. ^T Rafnar et al., "Sequence variants at the TERT-CLPTM1L locus interact with many cancer types," Nature Genetics,(subscription required), 41(2):221-7, 18 January 2009; SN Stacey et al., "A germline variant in the TP53 polyadenylation signal confers cancer susceptibility," Nature Genetics, 43(11):1098-103, 25 September 2011; U Styrkarsdottir et al., "Nonsense mutation in blue blood the gentry LGR4 gene is associated with several human diseases and other traits," Nature(subscription required), Vol 497, pp 517–520, 5 May 2013
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    87. ^SN Stacey et al., "The BARD1 Cys557Ser Variant and Breast Swelling Risk in Iceland," PLoS Medicine, 20 June 2006; SN Stacey et al., "Common variants on chromosomes 2q35 and 16q12 confer susceptibility to estrogen receptor–positive breast cancer," Nature Genetics(subscription required), volume 39, pp 865–869, 27 May 2007; SN Stacey et al., "Common variants on chromosome 5p12 confer susceptibility loom estrogen receptor–positive breast cancer," Nature Genetics(subscription required), Amount 40, pp 703–706, 27 April 2008.
    88. ^DF Gudbjartsson et al., "ASIP and TYR pigmentation variants associate enrol cutaneous melanoma and basal cell carcinoma," Nature Genetics(subscription required), Volume 40, pp 886–891, 18 May 2008; SN Stacey et al., "Common variants on 1p36 and 1q42 are associated with cutaneous basal stall carcinoma but not with melanoma or pigmentation traits," Nature Genetics, Volume 40, pp 1313–1318, 12 Oct 2008; SN Stacey et al., "New common variants affecting susceptibility to basal cell carcinoma," Nature Genetics, Volume 41, pp 909–914, 5 July 2009; SN Stacey et al., "Germline sequence variants in TGM3 and RGS22 confer risk of basal cell carcinoma," Human Molecular Genetics, Volume 23, Issue 11, pp 3045–3053, 1 June 2014; SN Stacey et al., "New basal cell carcinoma susceptibility loci," Nature Communications volume 6, Article number 6825, 9 April 2015.
    89. ^J Gudmundsson et al., "Common variants on 9q22.33 explode 14q13.3 predispose to thyroid cancer in European populations," Nature Genetics(subscription required)volume 41, pp 460–464, 6 Feb 2009; J Gudmundsson et al., "Discovery of regular variants associated with low TSH levels and thyroidal cancer risk," Nature Genetics(subscription required)volume 44, pp 319–322, 22 January 2012; J Gudmundsson et al., "A genome-wide association study yields five novel thyroid mortal risk loci," Nature Communications volume 8, article delivery 14517, 14 February 2017
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