Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained
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{"title"=>"Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained", "type"=>"journal", "authors"=>[{"first_name"=>"Ying", "last_name"=>"Wu", "scopus_author_id"=>"36505250600"}, {"first_name"=>"Lindsay L.", "last_name"=>"Waite", "scopus_author_id"=>"54938433600"}, {"first_name"=>"Anne U.", "last_name"=>"Jackson", "scopus_author_id"=>"7402785538"}, {"first_name"=>"Wayne H.H.", "last_name"=>"Sheu", "scopus_author_id"=>"57191058802"}, {"first_name"=>"Steven", "last_name"=>"Buyske", "scopus_author_id"=>"6602253579"}, {"first_name"=>"Devin", "last_name"=>"Absher", "scopus_author_id"=>"57198406019"}, {"first_name"=>"Donna K.", "last_name"=>"Arnett", "scopus_author_id"=>"7101719250"}, {"first_name"=>"Eric", "last_name"=>"Boerwinkle", "scopus_author_id"=>"7102087489"}, {"first_name"=>"Lori L.", "last_name"=>"Bonnycastle", "scopus_author_id"=>"6602395515"}, {"first_name"=>"Cara L.", "last_name"=>"Carty", "scopus_author_id"=>"57196028096"}, {"first_name"=>"Iona", "last_name"=>"Cheng", "scopus_author_id"=>"8646125400"}, {"first_name"=>"Barbara", "last_name"=>"Cochran", "scopus_author_id"=>"47760980400"}, {"first_name"=>"Damien C.", "last_name"=>"Croteau-Chonka", "scopus_author_id"=>"36056092200"}, {"first_name"=>"Logan", "last_name"=>"Dumitrescu", "scopus_author_id"=>"36767088000"}, {"first_name"=>"Charles B.", "last_name"=>"Eaton", "scopus_author_id"=>"35236601800"}, {"first_name"=>"Nora", "last_name"=>"Franceschini", "scopus_author_id"=>"7006270916"}, {"first_name"=>"Xiuqing", "last_name"=>"Guo", "scopus_author_id"=>"7404330868"}, {"first_name"=>"Brian E.", "last_name"=>"Henderson", "scopus_author_id"=>"55659755700"}, {"first_name"=>"Lucia A.", "last_name"=>"Hindorff", "scopus_author_id"=>"6602543812"}, {"first_name"=>"Eric", "last_name"=>"Kim", "scopus_author_id"=>"57199802836"}, {"first_name"=>"Leena", "last_name"=>"Kinnunen", "scopus_author_id"=>"7004228974"}, {"first_name"=>"Pirjo", "last_name"=>"Komulainen", "scopus_author_id"=>"57200311636"}, {"first_name"=>"Wen Jane", "last_name"=>"Lee", "scopus_author_id"=>"18634425500"}, {"first_name"=>"Loic", "last_name"=>"Le Marchand", "scopus_author_id"=>"7006229986"}, {"first_name"=>"Yi", "last_name"=>"Lin", "scopus_author_id"=>"53264165800"}, {"first_name"=>"Jaana", "last_name"=>"Lindström", "scopus_author_id"=>"55646081100"}, {"first_name"=>"Oddgeir", "last_name"=>"Lingaas-Holmen", "scopus_author_id"=>"55646837900"}, {"first_name"=>"Sabrina L.", "last_name"=>"Mitchell", "scopus_author_id"=>"25960188200"}, {"first_name"=>"Narisu", "last_name"=>"Narisu", "scopus_author_id"=>"57200401692"}, {"first_name"=>"Jennifer G.", "last_name"=>"Robinson", "scopus_author_id"=>"13604710300"}, {"first_name"=>"Fred", "last_name"=>"Schumacher", "scopus_author_id"=>"56386979100"}, {"first_name"=>"Alena", "last_name"=>"Stančáková", "scopus_author_id"=>"24175240900"}, {"first_name"=>"Jouko", "last_name"=>"Sundvall", "scopus_author_id"=>"6603627266"}, {"first_name"=>"Yun Ju", "last_name"=>"Sung", "scopus_author_id"=>"15045904600"}, {"first_name"=>"Amy J.", "last_name"=>"Swift", "scopus_author_id"=>"55801768400"}, {"first_name"=>"Wen Chang", "last_name"=>"Wang", "scopus_author_id"=>"12144015000"}, {"first_name"=>"Lynne", "last_name"=>"Wilkens", "scopus_author_id"=>"7007036544"}, {"first_name"=>"Tom", "last_name"=>"Wilsgaard", "scopus_author_id"=>"6602674711"}, {"first_name"=>"Alicia M.", "last_name"=>"Young", "scopus_author_id"=>"8250395400"}, {"first_name"=>"Linda S.", "last_name"=>"Adair", "scopus_author_id"=>"7005651928"}, {"first_name"=>"Christie M.", "last_name"=>"Ballantyne", "scopus_author_id"=>"7101711066"}, {"first_name"=>"Petra", "last_name"=>"Bůžková", "scopus_author_id"=>"23093239700"}, {"first_name"=>"Aravinda", "last_name"=>"Chakravarti", "scopus_author_id"=>"35355137200"}, {"first_name"=>"Francis S.", "last_name"=>"Collins", "scopus_author_id"=>"55574146000"}, {"first_name"=>"David", "last_name"=>"Duggan", "scopus_author_id"=>"34971014200"}, {"first_name"=>"Alan B.", "last_name"=>"Feranil", "scopus_author_id"=>"35231271400"}, {"first_name"=>"Low Tone", "last_name"=>"Ho", "scopus_author_id"=>"57129944800"}, {"first_name"=>"Yi Jen", "last_name"=>"Hung", "scopus_author_id"=>"56410394400"}, {"first_name"=>"Steven C.", "last_name"=>"Hunt", "scopus_author_id"=>"7402383343"}, {"first_name"=>"Kristian", "last_name"=>"Hveem", "scopus_author_id"=>"6701610017"}, {"first_name"=>"Jyh Ming J.", "last_name"=>"Juang", "scopus_author_id"=>"7202725945"}, {"first_name"=>"Antero Y.", "last_name"=>"Kesäniemi", "scopus_author_id"=>"55667210200"}, {"first_name"=>"Johanna", "last_name"=>"Kuusisto", "scopus_author_id"=>"55122317600"}, {"first_name"=>"Markku", "last_name"=>"Laakso", "scopus_author_id"=>"36078643000"}, {"first_name"=>"Timo A.", "last_name"=>"Lakka", "scopus_author_id"=>"7007104204"}, {"first_name"=>"I. Te", "last_name"=>"Lee", "scopus_author_id"=>"25825229100"}, {"first_name"=>"Mark F.", "last_name"=>"Leppert", "scopus_author_id"=>"35351313000"}, {"first_name"=>"Tara C.", "last_name"=>"Matise", "scopus_author_id"=>"7003415423"}, {"first_name"=>"Leena", "last_name"=>"Moilanen", "scopus_author_id"=>"57195387017"}, {"first_name"=>"Inger", "last_name"=>"Njølstad", "scopus_author_id"=>"6701604311"}, {"first_name"=>"Ulrike", "last_name"=>"Peters", "scopus_author_id"=>"7101680952"}, {"first_name"=>"Thomas", "last_name"=>"Quertermous", "scopus_author_id"=>"7005466084"}, {"first_name"=>"Rainer", "last_name"=>"Rauramaa", "scopus_author_id"=>"7006315020"}, {"first_name"=>"Jerome I.", "last_name"=>"Rotter", "scopus_author_id"=>"56284453500"}, {"first_name"=>"Jouko", "last_name"=>"Saramies", "scopus_author_id"=>"16426379000"}, {"first_name"=>"Jaakko", "last_name"=>"Tuomilehto", "scopus_author_id"=>"16140703200"}, {"first_name"=>"Matti", "last_name"=>"Uusitupa", "scopus_author_id"=>"35372209700"}, {"first_name"=>"Tzung Dau", "last_name"=>"Wang", "scopus_author_id"=>"7405566618"}, {"first_name"=>"Michael", "last_name"=>"Boehnke", "scopus_author_id"=>"7005423657"}, {"first_name"=>"Christopher A.", "last_name"=>"Haiman", "scopus_author_id"=>"6701722861"}, {"first_name"=>"Yii Der I.", "last_name"=>"Chen", "scopus_author_id"=>"8145846200"}, {"first_name"=>"Charles", "last_name"=>"Kooperberg", "scopus_author_id"=>"56758746100"}, {"first_name"=>"Themistocles L.", "last_name"=>"Assimes", "scopus_author_id"=>"56425902800"}, {"first_name"=>"Dana C.", "last_name"=>"Crawford", "scopus_author_id"=>"7403085570"}, {"first_name"=>"Chao A.", "last_name"=>"Hsiung", "scopus_author_id"=>"7006014026"}, {"first_name"=>"Kari E.", "last_name"=>"North", "scopus_author_id"=>"7006800602"}, {"first_name"=>"Karen L.", "last_name"=>"Mohlke", "scopus_author_id"=>"6602935932"}], "year"=>2013, "source"=>"PLoS Genetics", "identifiers"=>{"sgr"=>"84875996758", "pmid"=>"23555291", "pui"=>"368694393", "isbn"=>"1553-7404 (Electronic)\\n1553-7390 (Linking)", "scopus"=>"2-s2.0-84875996758", "doi"=>"10.1371/journal.pgen.1003379", "issn"=>"15537390"}, "id"=>"a5e41d02-c9e8-35a4-9394-9ec3069e3be7", "abstract"=>"Genome-wide association studies (GWAS) have identified ~100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at P<1 × 10(-4) in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at PCSK9 and APOA5. Trans-ethnic analyses narrowed the signals to smaller sets of variants at GCKR, PPP1R3B, ABO, LCAT, and ABCA1. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.", "link"=>"http://www.mendeley.com/research/transethnic-finemapping-lipid-loci-identifies-populationspecific-signals-allelic-heterogeneity-incre", "reader_count"=>82, "reader_count_by_academic_status"=>{"Professor > Associate Professor"=>9, "Librarian"=>2, "Student > Doctoral Student"=>6, "Researcher"=>26, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>2, "Other"=>4, "Student > Master"=>5, "Student > Bachelor"=>4, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_user_role"=>{"Professor > Associate Professor"=>9, "Librarian"=>2, "Student > Doctoral Student"=>6, "Researcher"=>26, "Student > Ph. D. Student"=>18, "Student > Postgraduate"=>2, "Other"=>4, "Student > Master"=>5, "Student > Bachelor"=>4, "Lecturer"=>1, "Lecturer > Senior Lecturer"=>1, "Professor"=>4}, "reader_count_by_subject_area"=>{"Unspecified"=>4, "Biochemistry, Genetics and Molecular Biology"=>10, "Agricultural and Biological Sciences"=>42, "Medicine and Dentistry"=>18, "Pharmacology, Toxicology and Pharmaceutical Science"=>1, "Social Sciences"=>2, "Computer Science"=>3, "Economics, Econometrics and Finance"=>2}, "reader_count_by_subdiscipline"=>{"Medicine and Dentistry"=>{"Medicine and Dentistry"=>18}, "Social Sciences"=>{"Social Sciences"=>2}, "Economics, Econometrics and Finance"=>{"Economics, Econometrics and Finance"=>2}, "Agricultural and Biological Sciences"=>{"Agricultural and Biological Sciences"=>42}, "Computer Science"=>{"Computer Science"=>3}, "Biochemistry, Genetics and Molecular Biology"=>{"Biochemistry, Genetics and Molecular Biology"=>10}, "Unspecified"=>{"Unspecified"=>4}, "Pharmacology, Toxicology and Pharmaceutical Science"=>{"Pharmacology, Toxicology and Pharmaceutical Science"=>1}}, "reader_count_by_country"=>{"Republic of Singapore"=>1, "Austria"=>1, "Netherlands"=>1, "United States"=>1, "Finland"=>1, "Switzerland"=>1, "Germany"=>1, "Spain"=>1}, "group_count"=>8}

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Figshare

  • {"files"=>["https://ndownloader.figshare.com/files/1008042"], "description"=>"a<p>LD (<i>r</i><sup>2</sup>/D′) with SNP showing the strongest evidence of association at each locus.</p>b<p>β: effect size from an additive model and corresponding to the effect allele, in the unit of mmol/L for HDL-C, LDL-C and natural log transformed TG.</p>c<p><i>P</i> values of sequential conditional analyses, in which we added the SNP with the strongest evidence of association into the regression model as a covariate and tested for the next strongest SNP until the strongest SNP showed a conditional <i>P</i> value>10<sup>−4</sup> and had no annotation suggesting potential function.</p>d<p>Variance explained by SNPs at each locus was estimated based on European samples.</p>e<p><i>P</i> values of initial association in African Americans and East Asians.</p>", "links"=>[], "tags"=>["loci", "signals"], "article_id"=>668608, "categories"=>["Genetics"], "users"=>["Ying Wu", "Lindsay L. Waite", "Anne U. Jackson", "Wayne H-H. Sheu", "Steven Buyske", "Devin Absher", "Donna K. Arnett", "Eric Boerwinkle", "Lori L. Bonnycastle", "Cara L. Carty", "Iona Cheng", "Barbara Cochran", "Damien C. Croteau-Chonka", "Logan Dumitrescu", "Charles B. Eaton", "Nora Franceschini", "Xiuqing Guo", "Brian E. Henderson", "Lucia A. Hindorff", "Eric Kim", "Leena Kinnunen", "Pirjo Komulainen", "Wen-Jane Lee", "Loic Le Marchand", "Yi Lin", "Jaana Lindström", "Oddgeir Lingaas-Holmen", "Sabrina L. Mitchell", "Narisu Narisu", "Jennifer G. Robinson", "Fred Schumacher", "Alena Stančáková", "Jouko Sundvall", "Yun-Ju Sung", "Amy J. Swift", "Wen-Chang Wang", "Lynne Wilkens", "Tom Wilsgaard", "Alicia M. Young", "Linda S. Adair", "Christie M. Ballantyne", "Petra Buzkova", "Aravinda Chakravarti", "Francis S. Collins", "David Duggan", "Alan B. Feranil", "Low-Tone Ho", "Yi-Jen Hung", "Steven C. Hunt", "Kristian Hveem", "Jyh-Ming J. Juang", "Antero Y. Kesäniemi", "Johanna Kuusisto", "Markku Laakso", "Timo A. Lakka", "I-Te Lee", "Mark F. Leppert", "Tara C. Matise", "Leena Moilanen", "Inger Njølstad", "Ulrike Peters", "Thomas Quertermous", "Rainer Rauramaa", "Jerome I. Rotter", "Jouko Saramies", "Jaakko Tuomilehto", "Matti Uusitupa", "Tzung-Dau Wang", "Michael Boehnke", "Christopher A. Haiman", "Yii-Der I. Chen", "Charles Kooperberg", "Themistocles L. Assimes", "Dana C. Crawford", "Chao A. Hsiung", "Kari E. North", "Karen L. Mohlke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003379.t002", "stats"=>{"downloads"=>1, "page_views"=>24, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lipid_loci_with_multiple_signals_in_Europeans_/668608", "title"=>"Lipid loci with multiple signals in Europeans.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-21 02:23:28"}
  • {"files"=>["https://ndownloader.figshare.com/files/1008123"], "description"=>"a<p>LD (r<sup>2</sup>/D′) with SNP showing the strongest evidence of association at each locus.</p>b<p>β: effect size from an additive model and corresponding to the effect allele, in the unit of mmol/L for HDL-C, LDL-C and natural log transformed TG.</p>c<p><i>P</i> values of sequential conditional analyses, in which we added the SNP with the strongest evidence of association into the regression model as a covariate and tested for the next strongest SNP until the strongest SNP showed a conditional <i>P</i> value>10<sup>−4</sup> and had no annotation suggesting potential function.</p>d<p>Variance explained was estimated based on PAGE samples (n = 5,593).</p>e<p><i>P</i> values of initial association in East Asians and Europeans.</p>f<p>Conditional analyses at LDL-C locus <i>PCSK9</i> were restricted to 5,593 PAGE samples because SNPs rs67608943 (Y142X), rs72646508 (L253F) and rs11591147 (R46L) were not polymorphic in HyperGEN samples.</p>", "links"=>[], "tags"=>["loci", "population-specific", "signals", "african"], "article_id"=>668684, "categories"=>["Genetics"], "users"=>["Ying Wu", "Lindsay L. Waite", "Anne U. Jackson", "Wayne H-H. Sheu", "Steven Buyske", "Devin Absher", "Donna K. Arnett", "Eric Boerwinkle", "Lori L. Bonnycastle", "Cara L. Carty", "Iona Cheng", "Barbara Cochran", "Damien C. Croteau-Chonka", "Logan Dumitrescu", "Charles B. Eaton", "Nora Franceschini", "Xiuqing Guo", "Brian E. Henderson", "Lucia A. Hindorff", "Eric Kim", "Leena Kinnunen", "Pirjo Komulainen", "Wen-Jane Lee", "Loic Le Marchand", "Yi Lin", "Jaana Lindström", "Oddgeir Lingaas-Holmen", "Sabrina L. Mitchell", "Narisu Narisu", "Jennifer G. Robinson", "Fred Schumacher", "Alena Stančáková", "Jouko Sundvall", "Yun-Ju Sung", "Amy J. Swift", "Wen-Chang Wang", "Lynne Wilkens", "Tom Wilsgaard", "Alicia M. Young", "Linda S. Adair", "Christie M. Ballantyne", "Petra Buzkova", "Aravinda Chakravarti", "Francis S. Collins", "David Duggan", "Alan B. Feranil", "Low-Tone Ho", "Yi-Jen Hung", "Steven C. Hunt", "Kristian Hveem", "Jyh-Ming J. Juang", "Antero Y. Kesäniemi", "Johanna Kuusisto", "Markku Laakso", "Timo A. Lakka", "I-Te Lee", "Mark F. Leppert", "Tara C. Matise", "Leena Moilanen", "Inger Njølstad", "Ulrike Peters", "Thomas Quertermous", "Rainer Rauramaa", "Jerome I. Rotter", "Jouko Saramies", "Jaakko Tuomilehto", "Matti Uusitupa", "Tzung-Dau Wang", "Michael Boehnke", "Christopher A. Haiman", "Yii-Der I. Chen", "Charles Kooperberg", "Themistocles L. Assimes", "Dana C. Crawford", "Chao A. Hsiung", "Kari E. North", "Karen L. Mohlke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003379.t001", "stats"=>{"downloads"=>1, "page_views"=>11, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lipid_loci_with_multiple_and_population_specific_signals_in_African_Americans_/668684", "title"=>"Lipid loci with multiple and population-specific signals in African Americans.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-21 02:24:44"}
  • {"files"=>["https://ndownloader.figshare.com/files/1007968"], "description"=>"a<p>LD (<i>r</i><sup>2</sup>/D′) with SNP showing the strongest evidence of association at each locus.</p>b<p>β: effect size from an additive model and corresponding to the effect allele, in the unit of mmol/L for HDL-C, LDL-C and natural log transformed TG.</p>c<p><i>P</i> values of sequential conditional analyses, in which we added the SNP with the strongest evidence of association into the regression model as a covariate and tested for the next strongest SNP until the strongest SNP showed a conditional <i>P</i> value>10<sup>−4</sup> and had no annotation suggesting potential function.</p>d<p>Variance explained by SNPs at each locus was estimated based on CLHNS samples (n = 1,716).</p>e<p><i>P</i> values of initial association in African Americans and Europeans.</p>", "links"=>[], "tags"=>["loci", "signals"], "article_id"=>668533, "categories"=>["Genetics"], "users"=>["Ying Wu", "Lindsay L. Waite", "Anne U. Jackson", "Wayne H-H. Sheu", "Steven Buyske", "Devin Absher", "Donna K. Arnett", "Eric Boerwinkle", "Lori L. Bonnycastle", "Cara L. Carty", "Iona Cheng", "Barbara Cochran", "Damien C. Croteau-Chonka", "Logan Dumitrescu", "Charles B. Eaton", "Nora Franceschini", "Xiuqing Guo", "Brian E. Henderson", "Lucia A. Hindorff", "Eric Kim", "Leena Kinnunen", "Pirjo Komulainen", "Wen-Jane Lee", "Loic Le Marchand", "Yi Lin", "Jaana Lindström", "Oddgeir Lingaas-Holmen", "Sabrina L. Mitchell", "Narisu Narisu", "Jennifer G. Robinson", "Fred Schumacher", "Alena Stančáková", "Jouko Sundvall", "Yun-Ju Sung", "Amy J. Swift", "Wen-Chang Wang", "Lynne Wilkens", "Tom Wilsgaard", "Alicia M. Young", "Linda S. Adair", "Christie M. Ballantyne", "Petra Buzkova", "Aravinda Chakravarti", "Francis S. Collins", "David Duggan", "Alan B. Feranil", "Low-Tone Ho", "Yi-Jen Hung", "Steven C. Hunt", "Kristian Hveem", "Jyh-Ming J. Juang", "Antero Y. Kesäniemi", "Johanna Kuusisto", "Markku Laakso", "Timo A. Lakka", "I-Te Lee", "Mark F. Leppert", "Tara C. Matise", "Leena Moilanen", "Inger Njølstad", "Ulrike Peters", "Thomas Quertermous", "Rainer Rauramaa", "Jerome I. Rotter", "Jouko Saramies", "Jaakko Tuomilehto", "Matti Uusitupa", "Tzung-Dau Wang", "Michael Boehnke", "Christopher A. Haiman", "Yii-Der I. Chen", "Charles Kooperberg", "Themistocles L. Assimes", "Dana C. Crawford", "Chao A. Hsiung", "Kari E. North", "Karen L. Mohlke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003379.t003", "stats"=>{"downloads"=>0, "page_views"=>20, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Lipid_loci_with_multiple_signals_in_East_Asians_/668533", "title"=>"Lipid loci with multiple signals in East Asians.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-21 02:22:13"}
  • {"files"=>["https://ndownloader.figshare.com/files/993374", "https://ndownloader.figshare.com/files/993376", "https://ndownloader.figshare.com/files/993383", "https://ndownloader.figshare.com/files/993385", "https://ndownloader.figshare.com/files/993389", "https://ndownloader.figshare.com/files/993392", "https://ndownloader.figshare.com/files/993393", "https://ndownloader.figshare.com/files/993394", "https://ndownloader.figshare.com/files/993395", "https://ndownloader.figshare.com/files/993396", "https://ndownloader.figshare.com/files/993397", "https://ndownloader.figshare.com/files/993398"], "description"=>"<div><p>Genome-wide association studies (GWAS) have identified ∼100 loci associated with blood lipid levels, but much of the trait heritability remains unexplained, and at most loci the identities of the trait-influencing variants remain unknown. We conducted a trans-ethnic fine-mapping study at 18, 22, and 18 GWAS loci on the Metabochip for their association with triglycerides (TG), high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C), respectively, in individuals of African American (n = 6,832), East Asian (n = 9,449), and European (n = 10,829) ancestry. We aimed to identify the variants with strongest association at each locus, identify additional and population-specific signals, refine association signals, and assess the relative significance of previously described functional variants. Among the 58 loci, 33 exhibited evidence of association at <i>P</i><1×10<sup>−4</sup> in at least one ancestry group. Sequential conditional analyses revealed that ten, nine, and four loci in African Americans, Europeans, and East Asians, respectively, exhibited two or more signals. At these loci, accounting for all signals led to a 1.3- to 1.8-fold increase in the explained phenotypic variance compared to the strongest signals. Distinct signals across ancestry groups were identified at <i>PCSK9</i> and <i>APOA5</i>. Trans-ethnic analyses narrowed the signals to smaller sets of variants at <i>GCKR</i>, <i>PPP1R3B</i>, <i>ABO</i>, <i>LCAT</i>, and <i>ABCA1</i>. Of 27 variants reported previously to have functional effects, 74% exhibited the strongest association at the respective signal. In conclusion, trans-ethnic high-density genotyping and analysis confirm the presence of allelic heterogeneity, allow the identification of population-specific variants, and limit the number of candidate SNPs for functional studies.</p> </div>", "links"=>[], "tags"=>["trans-ethnic", "fine-mapping", "lipid", "loci", "identifies", "population-specific", "signals", "allelic", "heterogeneity", "variance", "explained"], "article_id"=>656870, "categories"=>["Genetics"], "users"=>["Ying Wu", "Lindsay L. Waite", "Anne U. Jackson", "Wayne H-H. Sheu", "Steven Buyske", "Devin Absher", "Donna K. Arnett", "Eric Boerwinkle", "Lori L. Bonnycastle", "Cara L. Carty", "Iona Cheng", "Barbara Cochran", "Damien C. Croteau-Chonka", "Logan Dumitrescu", "Charles B. Eaton", "Nora Franceschini", "Xiuqing Guo", "Brian E. Henderson", "Lucia A. Hindorff", "Eric Kim", "Leena Kinnunen", "Pirjo Komulainen", "Wen-Jane Lee", "Loic Le Marchand", "Yi Lin", "Jaana Lindström", "Oddgeir Lingaas-Holmen", "Sabrina L. Mitchell", "Narisu Narisu", "Jennifer G. Robinson", "Fred Schumacher", "Alena Stančáková", "Jouko Sundvall", "Yun-Ju Sung", "Amy J. Swift", "Wen-Chang Wang", "Lynne Wilkens", "Tom Wilsgaard", "Alicia M. Young", "Linda S. Adair", "Christie M. Ballantyne", "Petra Buzkova", "Aravinda Chakravarti", "Francis S. Collins", "David Duggan", "Alan B. Feranil", "Low-Tone Ho", "Yi-Jen Hung", "Steven C. Hunt", "Kristian Hveem", "Jyh-Ming J. Juang", "Antero Y. Kesäniemi", "Johanna Kuusisto", "Markku Laakso", "Timo A. Lakka", "I-Te Lee", "Mark F. Leppert", "Tara C. Matise", "Leena Moilanen", "Inger Njølstad", "Ulrike Peters", "Thomas Quertermous", "Rainer Rauramaa", "Jerome I. Rotter", "Jouko Saramies", "Jaakko Tuomilehto", "Matti Uusitupa", "Tzung-Dau Wang", "Michael Boehnke", "Christopher A. Haiman", "Yii-Der I. Chen", "Charles Kooperberg", "Themistocles L. Assimes", "Dana C. Crawford", "Chao A. Hsiung", "Kari E. North", "Karen L. Mohlke"], "doi"=>["https://dx.doi.org/10.1371/journal.pgen.1003379.s001", "https://dx.doi.org/10.1371/journal.pgen.1003379.s002", "https://dx.doi.org/10.1371/journal.pgen.1003379.s003", "https://dx.doi.org/10.1371/journal.pgen.1003379.s004", "https://dx.doi.org/10.1371/journal.pgen.1003379.s005", "https://dx.doi.org/10.1371/journal.pgen.1003379.s006", "https://dx.doi.org/10.1371/journal.pgen.1003379.s007", "https://dx.doi.org/10.1371/journal.pgen.1003379.s008", "https://dx.doi.org/10.1371/journal.pgen.1003379.s009", "https://dx.doi.org/10.1371/journal.pgen.1003379.s010", "https://dx.doi.org/10.1371/journal.pgen.1003379.s011", "https://dx.doi.org/10.1371/journal.pgen.1003379.s012"], "stats"=>{"downloads"=>105, "page_views"=>25, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/Trans_Ethnic_Fine_Mapping_of_Lipid_Loci_Identifies_Population_Specific_Signals_and_Allelic_Heterogeneity_That_Increases_the_Trait_Variance_Explained__/656870", "title"=>"Trans-Ethnic Fine-Mapping of Lipid Loci Identifies Population-Specific Signals and Allelic Heterogeneity That Increases the Trait Variance Explained", "pos_in_sequence"=>0, "defined_type"=>4, "published_date"=>"2013-03-22 03:00:48"}
  • {"files"=>["https://ndownloader.figshare.com/files/1007894"], "description"=>"a<p><i>P</i> meta: <i>P</i> values from meta-analysis combining samples of African American, East Asian and European ancestries.</p>b<p>Direction: effect direction of each individual studies in the order of ARIC, MEC, WHI batch1, WHI batch2, HyperGEN, CLHNS, TAICHI, Finnish T2D, Finnish unaffected, Norwegian T2D and Norwegian unaffected.</p>c<p><i>P</i> het: <i>P</i> values for heterogeneity, indicating whether observed effect sizes are homogeneous across ancestry samples.</p>d<p><i>I</i><sup>2</sup>: index of the degree of heterogeneity.</p>", "links"=>[], "tags"=>["fine-mapping", "narrowed"], "article_id"=>668451, "categories"=>["Genetics"], "users"=>["Ying Wu", "Lindsay L. Waite", "Anne U. Jackson", "Wayne H-H. Sheu", "Steven Buyske", "Devin Absher", "Donna K. Arnett", "Eric Boerwinkle", "Lori L. Bonnycastle", "Cara L. Carty", "Iona Cheng", "Barbara Cochran", "Damien C. Croteau-Chonka", "Logan Dumitrescu", "Charles B. Eaton", "Nora Franceschini", "Xiuqing Guo", "Brian E. Henderson", "Lucia A. Hindorff", "Eric Kim", "Leena Kinnunen", "Pirjo Komulainen", "Wen-Jane Lee", "Loic Le Marchand", "Yi Lin", "Jaana Lindström", "Oddgeir Lingaas-Holmen", "Sabrina L. Mitchell", "Narisu Narisu", "Jennifer G. Robinson", "Fred Schumacher", "Alena Stančáková", "Jouko Sundvall", "Yun-Ju Sung", "Amy J. Swift", "Wen-Chang Wang", "Lynne Wilkens", "Tom Wilsgaard", "Alicia M. Young", "Linda S. Adair", "Christie M. Ballantyne", "Petra Buzkova", "Aravinda Chakravarti", "Francis S. Collins", "David Duggan", "Alan B. Feranil", "Low-Tone Ho", "Yi-Jen Hung", "Steven C. Hunt", "Kristian Hveem", "Jyh-Ming J. Juang", "Antero Y. Kesäniemi", "Johanna Kuusisto", "Markku Laakso", "Timo A. Lakka", "I-Te Lee", "Mark F. Leppert", "Tara C. Matise", "Leena Moilanen", "Inger Njølstad", "Ulrike Peters", "Thomas Quertermous", "Rainer Rauramaa", "Jerome I. Rotter", "Jouko Saramies", "Jaakko Tuomilehto", "Matti Uusitupa", "Tzung-Dau Wang", "Michael Boehnke", "Christopher A. Haiman", "Yii-Der I. Chen", "Charles Kooperberg", "Themistocles L. Assimes", "Dana C. Crawford", "Chao A. Hsiung", "Kari E. North", "Karen L. Mohlke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003379.t004", "stats"=>{"downloads"=>0, "page_views"=>14, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Trans_ethnic_fine_mapping_narrowed_the_association_signals_/668451", "title"=>"Trans-ethnic fine-mapping narrowed the association signals.", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-21 02:20:51"}
  • {"files"=>["https://ndownloader.figshare.com/files/1007811"], "description"=>"*<p>AA, African American; EUR, European; ASN, East Asian.</p>", "links"=>[], "tags"=>["variants", "exhibited", "strongest"], "article_id"=>668373, "categories"=>["Genetics"], "users"=>["Ying Wu", "Lindsay L. Waite", "Anne U. Jackson", "Wayne H-H. Sheu", "Steven Buyske", "Devin Absher", "Donna K. Arnett", "Eric Boerwinkle", "Lori L. Bonnycastle", "Cara L. Carty", "Iona Cheng", "Barbara Cochran", "Damien C. Croteau-Chonka", "Logan Dumitrescu", "Charles B. Eaton", "Nora Franceschini", "Xiuqing Guo", "Brian E. Henderson", "Lucia A. Hindorff", "Eric Kim", "Leena Kinnunen", "Pirjo Komulainen", "Wen-Jane Lee", "Loic Le Marchand", "Yi Lin", "Jaana Lindström", "Oddgeir Lingaas-Holmen", "Sabrina L. Mitchell", "Narisu Narisu", "Jennifer G. Robinson", "Fred Schumacher", "Alena Stančáková", "Jouko Sundvall", "Yun-Ju Sung", "Amy J. Swift", "Wen-Chang Wang", "Lynne Wilkens", "Tom Wilsgaard", "Alicia M. Young", "Linda S. Adair", "Christie M. Ballantyne", "Petra Buzkova", "Aravinda Chakravarti", "Francis S. Collins", "David Duggan", "Alan B. Feranil", "Low-Tone Ho", "Yi-Jen Hung", "Steven C. Hunt", "Kristian Hveem", "Jyh-Ming J. Juang", "Antero Y. Kesäniemi", "Johanna Kuusisto", "Markku Laakso", "Timo A. Lakka", "I-Te Lee", "Mark F. Leppert", "Tara C. Matise", "Leena Moilanen", "Inger Njølstad", "Ulrike Peters", "Thomas Quertermous", "Rainer Rauramaa", "Jerome I. Rotter", "Jouko Saramies", "Jaakko Tuomilehto", "Matti Uusitupa", "Tzung-Dau Wang", "Michael Boehnke", "Christopher A. Haiman", "Yii-Der I. Chen", "Charles Kooperberg", "Themistocles L. Assimes", "Dana C. Crawford", "Chao A. Hsiung", "Kari E. North", "Karen L. Mohlke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003379.t005", "stats"=>{"downloads"=>5, "page_views"=>9, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Reported_functional_variants_exhibited_the_strongest_association_at_a_signal_P_8722_4_/668373", "title"=>"Reported functional variants exhibited the strongest association at a signal (<i>P</i><10<sup>−4</sup>).", "pos_in_sequence"=>0, "defined_type"=>3, "published_date"=>"2013-03-21 02:19:33"}
  • {"files"=>["https://ndownloader.figshare.com/files/993368"], "description"=>"<p>Association in Europeans (A), East Asians (B), African Americans (C) and in a combined trans-ethnic meta-analysis (D). Index SNP rs6601299 colored in purple is the variant showing strongest evidence of association in the combined trans-ethnic meta-analysis.</p>", "links"=>[], "tags"=>["high-density", "genotyping", "narrows", "hdl-c", "locus"], "article_id"=>656865, "categories"=>["Genetics"], "users"=>["Ying Wu", "Lindsay L. Waite", "Anne U. Jackson", "Wayne H-H. Sheu", "Steven Buyske", "Devin Absher", "Donna K. Arnett", "Eric Boerwinkle", "Lori L. Bonnycastle", "Cara L. Carty", "Iona Cheng", "Barbara Cochran", "Damien C. Croteau-Chonka", "Logan Dumitrescu", "Charles B. Eaton", "Nora Franceschini", "Xiuqing Guo", "Brian E. Henderson", "Lucia A. Hindorff", "Eric Kim", "Leena Kinnunen", "Pirjo Komulainen", "Wen-Jane Lee", "Loic Le Marchand", "Yi Lin", "Jaana Lindström", "Oddgeir Lingaas-Holmen", "Sabrina L. Mitchell", "Narisu Narisu", "Jennifer G. Robinson", "Fred Schumacher", "Alena Stančáková", "Jouko Sundvall", "Yun-Ju Sung", "Amy J. Swift", "Wen-Chang Wang", "Lynne Wilkens", "Tom Wilsgaard", "Alicia M. Young", "Linda S. Adair", "Christie M. Ballantyne", "Petra Buzkova", "Aravinda Chakravarti", "Francis S. Collins", "David Duggan", "Alan B. Feranil", "Low-Tone Ho", "Yi-Jen Hung", "Steven C. Hunt", "Kristian Hveem", "Jyh-Ming J. Juang", "Antero Y. Kesäniemi", "Johanna Kuusisto", "Markku Laakso", "Timo A. Lakka", "I-Te Lee", "Mark F. Leppert", "Tara C. Matise", "Leena Moilanen", "Inger Njølstad", "Ulrike Peters", "Thomas Quertermous", "Rainer Rauramaa", "Jerome I. Rotter", "Jouko Saramies", "Jaakko Tuomilehto", "Matti Uusitupa", "Tzung-Dau Wang", "Michael Boehnke", "Christopher A. Haiman", "Yii-Der I. Chen", "Charles Kooperberg", "Themistocles L. Assimes", "Dana C. Crawford", "Chao A. Hsiung", "Kari E. North", "Karen L. Mohlke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003379.g002", "stats"=>{"downloads"=>1, "page_views"=>38, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_Trans_ethnic_high_density_genotyping_narrows_the_association_signal_at_the_HDL_C_locus_PPP1R3B_/656865", "title"=>"Trans-ethnic high-density genotyping narrows the association signal at the HDL-C locus <i>PPP1R3B</i>.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-22 03:00:03"}
  • {"files"=>["https://ndownloader.figshare.com/files/993366"], "description"=>"<p>Initial association in the main analysis (A). Residual association in sequential conditional analysis by sequentially adding the lead SNPs into the regression model (B–G). Each SNP was colored according to its LD (<i>r<sup>2</sup></i>) in the PAGE consortium, with the strongest SNP colored in purple and symbols designating genomic annotation defined in the ‘annotation key’. Genomic coordinates refer to build 36 (hg18).</p>", "links"=>[], "tags"=>["locus", "exhibited", "signals", "african"], "article_id"=>656863, "categories"=>["Genetics"], "users"=>["Ying Wu", "Lindsay L. Waite", "Anne U. Jackson", "Wayne H-H. Sheu", "Steven Buyske", "Devin Absher", "Donna K. Arnett", "Eric Boerwinkle", "Lori L. Bonnycastle", "Cara L. Carty", "Iona Cheng", "Barbara Cochran", "Damien C. Croteau-Chonka", "Logan Dumitrescu", "Charles B. Eaton", "Nora Franceschini", "Xiuqing Guo", "Brian E. Henderson", "Lucia A. Hindorff", "Eric Kim", "Leena Kinnunen", "Pirjo Komulainen", "Wen-Jane Lee", "Loic Le Marchand", "Yi Lin", "Jaana Lindström", "Oddgeir Lingaas-Holmen", "Sabrina L. Mitchell", "Narisu Narisu", "Jennifer G. Robinson", "Fred Schumacher", "Alena Stančáková", "Jouko Sundvall", "Yun-Ju Sung", "Amy J. Swift", "Wen-Chang Wang", "Lynne Wilkens", "Tom Wilsgaard", "Alicia M. Young", "Linda S. Adair", "Christie M. Ballantyne", "Petra Buzkova", "Aravinda Chakravarti", "Francis S. Collins", "David Duggan", "Alan B. Feranil", "Low-Tone Ho", "Yi-Jen Hung", "Steven C. Hunt", "Kristian Hveem", "Jyh-Ming J. Juang", "Antero Y. Kesäniemi", "Johanna Kuusisto", "Markku Laakso", "Timo A. Lakka", "I-Te Lee", "Mark F. Leppert", "Tara C. Matise", "Leena Moilanen", "Inger Njølstad", "Ulrike Peters", "Thomas Quertermous", "Rainer Rauramaa", "Jerome I. Rotter", "Jouko Saramies", "Jaakko Tuomilehto", "Matti Uusitupa", "Tzung-Dau Wang", "Michael Boehnke", "Christopher A. Haiman", "Yii-Der I. Chen", "Charles Kooperberg", "Themistocles L. Assimes", "Dana C. Crawford", "Chao A. Hsiung", "Kari E. North", "Karen L. Mohlke"], "doi"=>"https://dx.doi.org/10.1371/journal.pgen.1003379.g001", "stats"=>{"downloads"=>2, "page_views"=>29, "likes"=>0}, "figshare_url"=>"https://figshare.com/articles/_LDL_C_locus_PCSK9_exhibited_seven_signals_in_African_Americans_/656863", "title"=>"LDL-C locus <i>PCSK9</i> exhibited seven signals in African Americans.", "pos_in_sequence"=>0, "defined_type"=>1, "published_date"=>"2013-03-22 02:59:29"}

PMC Usage Stats | Further Information

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Relative Metric

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