Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population
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{"title"=>"Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population", "type"=>"journal", "authors"=>[{"first_name"=>"Elaine T.", "last_name"=>"Lim", "scopus_author_id"=>"55177996200"}, {"first_name"=>"Peter", "last_name"=>"Würtz", "scopus_author_id"=>"54879856600"}, {"first_name"=>"Aki S.", "last_name"=>"Havulinna", "scopus_author_id"=>"13403065100"}, {"first_name"=>"Priit", "last_name"=>"Palta", "scopus_author_id"=>"23012599400"}, {"first_name"=>"Taru", "last_name"=>"Tukiainen", "scopus_author_id"=>"24598298300"}, {"first_name"=>"Karola", "last_name"=>"Rehnström", "scopus_author_id"=>"6507963198"}, {"first_name"=>"Tõnu", "last_name"=>"Esko", "scopus_author_id"=>"26648246800"}, {"first_name"=>"Reedik", "last_name"=>"Mägi", "scopus_author_id"=>"56813518300"}, {"first_name"=>"Michael", "last_name"=>"Inouye", "scopus_author_id"=>"22953271700"}, {"first_name"=>"Tuuli", "last_name"=>"Lappalainen", "scopus_author_id"=>"14323311700"}, {"first_name"=>"Yingleong", "last_name"=>"Chan", "scopus_author_id"=>"54881777300"}, {"first_name"=>"Rany M.", "last_name"=>"Salem", "scopus_author_id"=>"8546484800"}, {"first_name"=>"Monkol", "last_name"=>"Lek", "scopus_author_id"=>"26639403100"}, {"first_name"=>"Jason", "last_name"=>"Flannick", "scopus_author_id"=>"8719247900"}, {"first_name"=>"Xueling", "last_name"=>"Sim", "scopus_author_id"=>"15069915400"}, {"first_name"=>"Alisa", "last_name"=>"Manning", "scopus_author_id"=>"15052094400"}, {"first_name"=>"Claes", "last_name"=>"Ladenvall", "scopus_author_id"=>"14066257800"}, {"first_name"=>"Suzannah", "last_name"=>"Bumpstead", "scopus_author_id"=>"22953004000"}, {"first_name"=>"Eija", "last_name"=>"Hämäläinen", "scopus_author_id"=>"35310343300"}, {"first_name"=>"Kristiina", "last_name"=>"Aalto", "scopus_author_id"=>"36951101700"}, {"first_name"=>"Mikael", "last_name"=>"Maksimow", "scopus_author_id"=>"6506135704"}, {"first_name"=>"Marko", "last_name"=>"Salmi", "scopus_author_id"=>"7006628975"}, {"first_name"=>"Stefan", "last_name"=>"Blankenberg", "scopus_author_id"=>"7004496618"}, {"first_name"=>"Diego", "last_name"=>"Ardissino", "scopus_author_id"=>"7005864114"}, {"first_name"=>"Svati", "last_name"=>"Shah", "scopus_author_id"=>"55460965000"}, {"first_name"=>"Benjamin", "last_name"=>"Horne", "scopus_author_id"=>"34769653600"}, {"first_name"=>"Ruth", "last_name"=>"McPherson", "scopus_author_id"=>"7102810960"}, {"first_name"=>"Gerald K.", "last_name"=>"Hovingh", "scopus_author_id"=>"6602780482"}, {"first_name"=>"Muredach P.", "last_name"=>"Reilly", "scopus_author_id"=>"7202322545"}, {"first_name"=>"Hugh", "last_name"=>"Watkins", "scopus_author_id"=>"7004286059"}, {"first_name"=>"Anuj", "last_name"=>"Goel", "scopus_author_id"=>"14323071100"}, {"first_name"=>"Martin", "last_name"=>"Farrall", "scopus_author_id"=>"7006468255"}, {"first_name"=>"Domenico", "last_name"=>"Girelli", "scopus_author_id"=>"7005655357"}, {"first_name"=>"Alex P.", "last_name"=>"Reiner", "scopus_author_id"=>"7101737386"}, {"first_name"=>"Nathan O.", "last_name"=>"Stitziel", "scopus_author_id"=>"6507357414"}, {"first_name"=>"Sekar", "last_name"=>"Kathiresan", "scopus_author_id"=>"6602176567"}, {"first_name"=>"Stacey", "last_name"=>"Gabriel", "scopus_author_id"=>"7202104113"}, {"first_name"=>"Jeffrey C.", "last_name"=>"Barrett", "scopus_author_id"=>"55628588612"}, {"first_name"=>"Terho", "last_name"=>"Lehtimäki", "scopus_author_id"=>"7006539182"}, {"first_name"=>"Markku", "last_name"=>"Laakso", "scopus_author_id"=>"36078643000"}, {"first_name"=>"Leif", "last_name"=>"Groop", "scopus_author_id"=>"21634758500"}, {"first_name"=>"Jaakko", "last_name"=>"Kaprio", "scopus_author_id"=>"35379599600"}, {"first_name"=>"Markus", "last_name"=>"Perola", "scopus_author_id"=>"7003719630"}, {"first_name"=>"Mark I.", "last_name"=>"McCarthy", "scopus_author_id"=>"7402061249"}, {"first_name"=>"Michael", "last_name"=>"Boehnke", "scopus_author_id"=>"7005423657"}, {"first_name"=>"David M.", "last_name"=>"Altshuler", "scopus_author_id"=>"7005798316"}, {"first_name"=>"Cecilia M.", "last_name"=>"Lindgren", "scopus_author_id"=>"7005443464"}, {"first_name"=>"Joel N.", "last_name"=>"Hirschhorn", "scopus_author_id"=>"7006710354"}, {"first_name"=>"Andres", "last_name"=>"Metspalu", "scopus_author_id"=>"7004697483"}, {"first_name"=>"Nelson B.", "last_name"=>"Freimer", "scopus_author_id"=>"7006012650"}, {"first_name"=>"Tanja", "last_name"=>"Zeller", "scopus_author_id"=>"8840941700"}, {"first_name"=>"Sirpa", "last_name"=>"Jalkanen", "scopus_author_id"=>"56040673700"}, {"first_name"=>"Seppo", "last_name"=>"Koskinen", "scopus_author_id"=>"7004428281"}, {"first_name"=>"Olli", "last_name"=>"Raitakari", "scopus_author_id"=>"7004828916"}, {"first_name"=>"Richard", "last_name"=>"Durbin", "scopus_author_id"=>"7102868950"}, {"first_name"=>"Daniel G.", "last_name"=>"MacArthur", "scopus_author_id"=>"7004309751"}, {"first_name"=>"Veikko", "last_name"=>"Salomaa", "scopus_author_id"=>"7004714461"}, {"first_name"=>"Samuli", "last_name"=>"Ripatti", "scopus_author_id"=>"6603009457"}, {"first_name"=>"Mark J.", "last_name"=>"Daly", "scopus_author_id"=>"7201456226"}, {"first_name"=>"Aarno", "last_name"=>"Palotie", "scopus_author_id"=>"7005614368"}], "year"=>2014, "source"=>"PLoS Genetics", "identifiers"=>{"pui"=>"373701248", "sgr"=>"84905460411", "pmid"=>"25078778", "scopus"=>"2-s2.0-84905460411", "isbn"=>"2201127891", "doi"=>"10.1371/journal.pgen.1004494", "issn"=>"15537404"}, "id"=>"a4d77719-c560-3d6f-9723-66a50af298cc", "abstract"=>"Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5-5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p<5×10⁻⁸) including splice variants in LPA that lowered plasma lipoprotein(a) levels (P = 1.5×10⁻¹¹⁷). Through accessing the national medical records of these participants, we evaluate the LPA finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10⁻⁴), demonstrating for the first time the correlation between very low levels of LPA in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Registers.", "link"=>"http://www.mendeley.com/research/distribution-medical-impact-lossoffunction-variants-finnish-founder-population", "reader_count"=>207, "reader_count_by_academic_status"=>{"Unspecified"=>5, "Professor > Associate Professor"=>12, "Librarian"=>2, "Researcher"=>59, "Student > Doctoral Student"=>8, "Student > Ph. D. Student"=>63, "Student > Postgraduate"=>9, "Student > Master"=>16, "Other"=>8, "Student > Bachelor"=>14, "Lecturer"=>1, "Professor"=>10}, "reader_count_by_user_role"=>{"Unspecified"=>5, "Professor > Associate Professor"=>12, "Librarian"=>2, "Researcher"=>59, "Student > Doctoral Student"=>8, "Student > Ph. D. Student"=>63, "Student > Postgraduate"=>9, "Student > Master"=>16, "Other"=>8, "Student > Bachelor"=>14, "Lecturer"=>1, "Professor"=>10}, "reader_count_by_subject_area"=>{"Unspecified"=>8, "Agricultural and Biological Sciences"=>104, "Computer Science"=>5, "Earth and Planetary Sciences"=>1, "Engineering"=>1, "Environmental Science"=>1, "Biochemistry, Genetics and Molecular Biology"=>38, "Mathematics"=>2, "Medicine and Dentistry"=>38, "Neuroscience"=>2, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Physics and Astronomy"=>1, "Psychology"=>1, "Social Sciences"=>2, "Immunology and Microbiology"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>38}, "Social Sciences"=>{"Social Sciences"=>2}, "Physics and Astronomy"=>{"Physics and Astronomy"=>1}, "Psychology"=>{"Psychology"=>1}, "Mathematics"=>{"Mathematics"=>2}, "Unspecified"=>{"Unspecified"=>8}, "Environmental Science"=>{"Environmental Science"=>1}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}, "Engineering"=>{"Engineering"=>1}, "Neuroscience"=>{"Neuroscience"=>2}, "Earth and Planetary Sciences"=>{"Earth and Planetary Sciences"=>1}, "Immunology and Microbiology"=>{"Immunology and Microbiology"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>104}, "Computer Science"=>{"Computer Science"=>5}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>38}}, "reader_count_by_country"=>{"Austria"=>1, "Netherlands"=>1, "Sweden"=>1, "Norway"=>1, "United States"=>2, "Finland"=>2, "United Kingdom"=>3, "Italy"=>1, "France"=>1}, "group_count"=>9}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1617178"], "description"=>"<p>The associations that are experiment-wide significant highlighted in bold. The discovery dataset is a subset from FINRISK and the replication datasets are from the Health2000 and Young Finns studies.</p><p>* The 2 splice variants in <i>LPA</i> were combined to obtain a composite <i>LPA</i> variant for the association analyses.</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Genome-wide association studies", "Evolutionary biology", "population genetics", "genetics", "Genetics of disease", "Genetic disorders", "Heredity", "Quantitative traits", "Human genetics", "Genetic association studies", "Gene disruption", "genomics", "phenotypes", "dataset"], "article_id"=>1123645, "categories"=>["Biological Sciences"], "users"=>["Elaine T. Lim", "Peter Würtz", "Aki S. Havulinna", "Priit Palta", "Taru Tukiainen", "Karola Rehnström", "Tõnu Esko", "Reedik Magi", "Michael Inouye", "Tuuli Lappalainen", "Yingleong Chan", "Rany M. Salem", "Monkol Lek", "Jason Flannick", "Xueling Sim", "Alisa Manning", "Claes Ladenvall", "Suzannah Bumpstead", "Eija Hamalainen", "Kristiina Aalto", "Mikael Maksimow", "Marko Salmi", "Stefan Blankenberg", "Diego Ardissino", "Svati Shah", "Benjamin Horne", "Ruth McPherson", "Gerald K. Hovingh", "Muredach P. Reilly", "Hugh Watkins", "Anuj Goel", "Martin Farrall", "Domenico Girelli", "Alex P. Reiner", "Nathan O. Stitziel", "Sekar Kathiresan", "Stacey Gabriel", "Jeffrey C. Barrett", "Terho Lehtimäki", "Markku Laakso", "Leif Groop", "Jaakko Kaprio", "Markus Perola", "Mark I. McCarthy", "Michael Boehnke", "David M. Altshuler", "Cecilia M. Lindgren", "Joel N. Hirschhorn", "Andres Metspalu", "Nelson B. Freimer", "Tanja Zeller", "Sirpa Jalkanen", "Seppo Koskinen", "Olli Raitakari", "Richard Durbin", "Daniel G. MacArthur", "Veikko Salomaa", "Samuli Ripatti", "Mark J. Daly", "Aarno Palotie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004494.t001", "stats"=>{"downloads"=>4, "page_views"=>6, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_List_of_top_association_results_from_the_discovery_dataset_with_p_8722_4_/1123645", "title"=>"List of top association results from the discovery dataset with p<2×10<sup>−4</sup>.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2014-07-31 03:18:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1617177"], "description"=>"<p>The cardiovascular diseases were defined as coronary heart disease (CHD), ischemic heart disease (IHD), heart failure (HF) or myocardial infarction (MI) from the various cohorts.</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Genome-wide association studies", "Evolutionary biology", "population genetics", "genetics", "Genetics of disease", "Genetic disorders", "Heredity", "Quantitative traits", "Human genetics", "Genetic association studies", "Gene disruption", "genomics", "phenotypes", "splice", "variants", "cardiovascular"], "article_id"=>1123643, "categories"=>["Biological Sciences"], "users"=>["Elaine T. Lim", "Peter Würtz", "Aki S. Havulinna", "Priit Palta", "Taru Tukiainen", "Karola Rehnström", "Tõnu Esko", "Reedik Magi", "Michael Inouye", "Tuuli Lappalainen", "Yingleong Chan", "Rany M. Salem", "Monkol Lek", "Jason Flannick", "Xueling Sim", "Alisa Manning", "Claes Ladenvall", "Suzannah Bumpstead", "Eija Hamalainen", "Kristiina Aalto", "Mikael Maksimow", "Marko Salmi", "Stefan Blankenberg", "Diego Ardissino", "Svati Shah", "Benjamin Horne", "Ruth McPherson", "Gerald K. Hovingh", "Muredach P. Reilly", "Hugh Watkins", "Anuj Goel", "Martin Farrall", "Domenico Girelli", "Alex P. Reiner", "Nathan O. Stitziel", "Sekar Kathiresan", "Stacey Gabriel", "Jeffrey C. Barrett", "Terho Lehtimäki", "Markku Laakso", "Leif Groop", "Jaakko Kaprio", "Markus Perola", "Mark I. McCarthy", "Michael Boehnke", "David M. Altshuler", "Cecilia M. Lindgren", "Joel N. Hirschhorn", "Andres Metspalu", "Nelson B. Freimer", "Tanja Zeller", "Sirpa Jalkanen", "Seppo Koskinen", "Olli Raitakari", "Richard Durbin", "Daniel G. MacArthur", "Veikko Salomaa", "Samuli Ripatti", "Mark J. Daly", "Aarno Palotie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004494.g003", "stats"=>{"downloads"=>1, "page_views"=>13, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Forest_plot_for_the_LPA_splice_variants_with_cardiovascular_diseases_/1123643", "title"=>"Forest plot for the <i>LPA</i> splice variants with cardiovascular diseases.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-31 03:18:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1617159"], "description"=>"<p>(A) Ratio of the number of LoF, missense and synonymous variants found in Finns versus NFEs with the ratios for LoF variants highlighted in red text and the ratios for synonymous variants in black. The p-values represent the probabilities of the excess of variable sites in Finns occurring by chance. The p-values in red represent the probabilities for the LoF variants, the p-values in blue represent the probabilities for the missense variants and the p-values in black represent the probabilities for the synonymous variants. (B) Percentage of variants that are LoF across the allele frequency spectrum, with the numbers indicating the percentage of LoF variants in Finns versus NFEs. The p-values represent the p-values from the hypergeometric test of whether the ratio of LoF variants differ from the ratio of synonymous variants in Finns compared to NFEs.</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Genome-wide association studies", "Evolutionary biology", "population genetics", "genetics", "Genetics of disease", "Genetic disorders", "Heredity", "Quantitative traits", "Human genetics", "Genetic association studies", "Gene disruption", "genomics", "phenotypes", "finns", "demonstrating", "proportionally", "deleterious", "low-frequency"], "article_id"=>1123633, "categories"=>["Biological Sciences"], "users"=>["Elaine T. Lim", "Peter Würtz", "Aki S. Havulinna", "Priit Palta", "Taru Tukiainen", "Karola Rehnström", "Tõnu Esko", "Reedik Magi", "Michael Inouye", "Tuuli Lappalainen", "Yingleong Chan", "Rany M. Salem", "Monkol Lek", "Jason Flannick", "Xueling Sim", "Alisa Manning", "Claes Ladenvall", "Suzannah Bumpstead", "Eija Hamalainen", "Kristiina Aalto", "Mikael Maksimow", "Marko Salmi", "Stefan Blankenberg", "Diego Ardissino", "Svati Shah", "Benjamin Horne", "Ruth McPherson", "Gerald K. Hovingh", "Muredach P. Reilly", "Hugh Watkins", "Anuj Goel", "Martin Farrall", "Domenico Girelli", "Alex P. Reiner", "Nathan O. Stitziel", "Sekar Kathiresan", "Stacey Gabriel", "Jeffrey C. Barrett", "Terho Lehtimäki", "Markku Laakso", "Leif Groop", "Jaakko Kaprio", "Markus Perola", "Mark I. McCarthy", "Michael Boehnke", "David M. Altshuler", "Cecilia M. Lindgren", "Joel N. Hirschhorn", "Andres Metspalu", "Nelson B. Freimer", "Tanja Zeller", "Sirpa Jalkanen", "Seppo Koskinen", "Olli Raitakari", "Richard Durbin", "Daniel G. MacArthur", "Veikko Salomaa", "Samuli Ripatti", "Mark J. Daly", "Aarno Palotie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004494.g001", "stats"=>{"downloads"=>2, "page_views"=>40, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Allele_frequency_spectrum_in_Finns_and_NFEs_demonstrating_that_Finns_have_proportionally_more_deleterious_rare_and_low_frequency_variants_/1123633", "title"=>"Allele frequency spectrum in Finns and NFEs, demonstrating that Finns have proportionally more deleterious rare and low-frequency variants.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-31 03:18:39"}
  • {"files"=>["https://ndownloader.figshare.com/files/1617208", "https://ndownloader.figshare.com/files/1617220", "https://ndownloader.figshare.com/files/1617221", "https://ndownloader.figshare.com/files/1617222", "https://ndownloader.figshare.com/files/1617223", "https://ndownloader.figshare.com/files/1617226", "https://ndownloader.figshare.com/files/1617227", "https://ndownloader.figshare.com/files/1617228", "https://ndownloader.figshare.com/files/1617229", "https://ndownloader.figshare.com/files/1617219", "https://ndownloader.figshare.com/files/1617218", "https://ndownloader.figshare.com/files/1617209", "https://ndownloader.figshare.com/files/1617210", "https://ndownloader.figshare.com/files/1617212", "https://ndownloader.figshare.com/files/1617213", "https://ndownloader.figshare.com/files/1617214", "https://ndownloader.figshare.com/files/1617215", "https://ndownloader.figshare.com/files/1617216", "https://ndownloader.figshare.com/files/1617217", "https://ndownloader.figshare.com/files/1617230"], "description"=>"<div><p>Exome sequencing studies in complex diseases are challenged by the allelic heterogeneity, large number and modest effect sizes of associated variants on disease risk and the presence of large numbers of neutral variants, even in phenotypically relevant genes. Isolated populations with recent bottlenecks offer advantages for studying rare variants in complex diseases as they have deleterious variants that are present at higher frequencies as well as a substantial reduction in rare neutral variation. To explore the potential of the Finnish founder population for studying low-frequency (0.5–5%) variants in complex diseases, we compared exome sequence data on 3,000 Finns to the same number of non-Finnish Europeans and discovered that, despite having fewer variable sites overall, the average Finn has more low-frequency loss-of-function variants and complete gene knockouts. We then used several well-characterized Finnish population cohorts to study the phenotypic effects of 83 enriched loss-of-function variants across 60 phenotypes in 36,262 Finns. Using a deep set of quantitative traits collected on these cohorts, we show 5 associations (p&lt;5×10<sup>−8</sup>) including splice variants in <i>LPA</i> that lowered plasma lipoprotein(a) levels (P = 1.5×10<sup>−117</sup>). Through accessing the national medical records of these participants, we evaluate the <i>LPA</i> finding via Mendelian randomization and confirm that these splice variants confer protection from cardiovascular disease (OR = 0.84, P = 3×10<sup>−4</sup>), demonstrating for the first time the correlation between very low levels of <i>LPA</i> in humans with potential therapeutic implications for cardiovascular diseases. More generally, this study articulates substantial advantages for studying the role of rare variation in complex phenotypes in founder populations like the Finns and by combining a unique population genetic history with data from large population cohorts and centralized research access to National Health Regis", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Genome-wide association studies", "Evolutionary biology", "population genetics", "genetics", "Genetics of disease", "Genetic disorders", "Heredity", "Quantitative traits", "Human genetics", "Genetic association studies", "Gene disruption", "genomics", "phenotypes", "loss-of-function", "variants", "finnish"], "article_id"=>1123668, "categories"=>["Biological Sciences"], "users"=>["Elaine T. Lim", "Peter Würtz", "Aki S. Havulinna", "Priit Palta", "Taru Tukiainen", "Karola Rehnström", "Tõnu Esko", "Reedik Magi", "Michael Inouye", "Tuuli Lappalainen", "Yingleong Chan", "Rany M. Salem", "Monkol Lek", "Jason Flannick", "Xueling Sim", "Alisa Manning", "Claes Ladenvall", "Suzannah Bumpstead", "Eija Hamalainen", "Kristiina Aalto", "Mikael Maksimow", "Marko Salmi", "Stefan Blankenberg", "Diego Ardissino", "Svati Shah", "Benjamin Horne", "Ruth McPherson", "Gerald K. Hovingh", "Muredach P. Reilly", "Hugh Watkins", "Anuj Goel", "Martin Farrall", "Domenico Girelli", "Alex P. Reiner", "Nathan O. Stitziel", "Sekar Kathiresan", "Stacey Gabriel", "Jeffrey C. Barrett", "Terho Lehtimäki", "Markku Laakso", "Leif Groop", "Jaakko Kaprio", "Markus Perola", "Mark I. McCarthy", "Michael Boehnke", "David M. Altshuler", "Cecilia M. Lindgren", "Joel N. Hirschhorn", "Andres Metspalu", "Nelson B. Freimer", "Tanja Zeller", "Sirpa Jalkanen", "Seppo Koskinen", "Olli Raitakari", "Richard Durbin", "Daniel G. MacArthur", "Veikko Salomaa", "Samuli Ripatti", "Mark J. Daly", "Aarno Palotie"], "doi"=>[nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil, nil], "stats"=>{"downloads"=>150, "page_views"=>39, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Distribution_and_Medical_Impact_of_Loss_of_Function_Variants_in_the_Finnish_Founder_Population/1123668", "title"=>"Distribution and Medical Impact of Loss-of-Function Variants in the Finnish Founder Population", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2015-04-12 17:44:36"}
  • {"files"=>["https://ndownloader.figshare.com/files/1617170"], "description"=>"<p>The analysis was performed from an initial set of exome sequences from Finns and NFEs, as well as the selection and survey of the 83 LoF variants across 60 quantitative traits and 13 disease categories.</p>", "links"=>[], "tags"=>["Computational biology", "genome analysis", "Genome-wide association studies", "Evolutionary biology", "population genetics", "genetics", "Genetics of disease", "Genetic disorders", "Heredity", "Quantitative traits", "Human genetics", "Genetic association studies", "Gene disruption", "genomics", "phenotypes"], "article_id"=>1123639, "categories"=>["Biological Sciences"], "users"=>["Elaine T. Lim", "Peter Würtz", "Aki S. Havulinna", "Priit Palta", "Taru Tukiainen", "Karola Rehnström", "Tõnu Esko", "Reedik Magi", "Michael Inouye", "Tuuli Lappalainen", "Yingleong Chan", "Rany M. Salem", "Monkol Lek", "Jason Flannick", "Xueling Sim", "Alisa Manning", "Claes Ladenvall", "Suzannah Bumpstead", "Eija Hamalainen", "Kristiina Aalto", "Mikael Maksimow", "Marko Salmi", "Stefan Blankenberg", "Diego Ardissino", "Svati Shah", "Benjamin Horne", "Ruth McPherson", "Gerald K. Hovingh", "Muredach P. Reilly", "Hugh Watkins", "Anuj Goel", "Martin Farrall", "Domenico Girelli", "Alex P. Reiner", "Nathan O. Stitziel", "Sekar Kathiresan", "Stacey Gabriel", "Jeffrey C. Barrett", "Terho Lehtimäki", "Markku Laakso", "Leif Groop", "Jaakko Kaprio", "Markus Perola", "Mark I. McCarthy", "Michael Boehnke", "David M. Altshuler", "Cecilia M. Lindgren", "Joel N. Hirschhorn", "Andres Metspalu", "Nelson B. Freimer", "Tanja Zeller", "Sirpa Jalkanen", "Seppo Koskinen", "Olli Raitakari", "Richard Durbin", "Daniel G. MacArthur", "Veikko Salomaa", "Samuli Ripatti", "Mark J. Daly", "Aarno Palotie"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1004494.g002", "stats"=>{"downloads"=>1, "page_views"=>15, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Study_design_figure_for_the_project_/1123639", "title"=>"Study design figure for the project.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2014-07-31 03:18:39"}

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{"start_date"=>"2014-01-01T00:00:00Z", "end_date"=>"2014-12-31T00:00:00Z", "subject_areas"=>[{"subject_area"=>"/Medicine and health sciences/Hematology", "average_usage"=>[256]}]}
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