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Author (up) Lu, X.; Peloso, G.M.; Liu, D.J.; Wu, Y.; Zhang, H.; Zhou, W.; Li, J.; Tang, C.S.-M.; Dorajoo, R.; Li, H.; Long, J.; Guo, X.; Xu, M.; Spracklen, C.N.; Chen, Y.; Liu, X.; Zhang, Y.; Khor, C.C.; Liu, J.; Sun, L.; Wang, L.; Gao, Y.-T.; Hu, Y.; Yu, K.; Wang, Y.; Cheung, C.Y.Y.; Wang, F.; Huang, J.; Fan, Q.; Cai, Q.; Chen, S.; Shi, J.; Yang, X.; Zhao, W.; Sheu, W.H.-H.; Cherny, S.S.; He, M.; Feranil, A.B.; Adair, L.S.; Gordon-Larsen, P.; Du, S.; Varma, R.; Chen, Y.-D.I.; Shu, X.-O.; Lam, K.S.L.; Wong, T.Y.; Ganesh, S.K.; Mo, Z.; Hveem, K.; Fritsche, L.G.; Nielsen, J.B.; Tse, H.-F.; Huo, Y.; Cheng, C.-Y.; Chen, Y.E.; Zheng, W.; Tai, E.S.; Gao, W.; Lin, X.; Huang, W.; Abecasis, G.; Kathiresan, S.; Mohlke, K.L.; Wu, T.; Sham, P.C.; Gu, D.; Willer, C.J. url  doi
  Title Exome chip meta-analysis identifies novel loci and East Asian-specific coding variants that contribute to lipid levels and coronary artery disease Type Meta-Analysis
  Year 2017 Publication Nature Genetics Abbreviated Journal Nat Genet  
  Volume 49 Issue 12 Pages 1722-1730  
  Keywords Asian Continental Ancestry Group/genetics; Coronary Artery Disease/ethnology/*genetics; Europe; European Continental Ancestry Group/genetics; Exome/*genetics; Far East; Gene Frequency; Genetic Predisposition to Disease/ethnology/*genetics; *Genetic Variation; Genome-Wide Association Study; Genotype; Humans; Lipid Metabolism/*genetics; Lipids/analysis  
  Abstract Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.  
  Address Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, Michigan, USA  
  Corporate Author GLGC Consortium Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1061-4036 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:29083407 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1957  
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Author (up) Wu, Y.; Waite, L.L.; Jackson, A.U.; Sheu, W.H.-H.; Buyske, S.; Absher, D.; Arnett, D.K.; Boerwinkle, E.; Bonnycastle, L.L.; Carty, C.L.; Cheng, I.; Cochran, B.; Croteau-Chonka, D.C.; Dumitrescu, L.; Eaton, C.B.; Franceschini, N.; Guo, X.; Henderson, B.E.; Hindorff, L.A.; Kim, E.; Kinnunen, L.; Komulainen, P.; Lee, W.-J.; Le Marchand, L.; Lin, Y.; Lindstrom, J.; Lingaas-Holmen, O.; Mitchell, S.L.; Narisu, N.; Robinson, J.G.; Schumacher, F.; Stancakova, A.; Sundvall, J.; Sung, Y.-J.; Swift, A.J.; Wang, W.-C.; Wilkens, L.; Wilsgaard, T.; Young, A.M.; Adair, L.S.; Ballantyne, C.M.; Buzkova, P.; Chakravarti, A.; Collins, F.S.; Duggan, D.; Feranil, A.B.; Ho, L.-T.; Hung, Y.-J.; Hunt, S.C.; Hveem, K.; Juang, J.-M.J.; Kesaniemi, A.Y.; Kuusisto, J.; Laakso, M.; Lakka, T.A.; Lee, I.-T.; Leppert, M.F.; Matise, T.C.; Moilanen, L.; Njolstad, I.; Peters, U.; Quertermous, T.; Rauramaa, R.; Rotter, J.I.; Saramies, J.; Tuomilehto, J.; Uusitupa, M.; Wang, T.-D.; Boehnke, M.; Haiman, C.A.; Chen, Y.-D.I.; Kooperberg, C.; Assimes, T.L.; Crawford, D.C.; Hsiung, C.A.; North, K.E.; Mohlke, K.L. url  doi
  Title Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained Type Journal Article
  Year 2013 Publication PLoS Genetics Abbreviated Journal PLoS Genet  
  Volume 9 Issue 3 Pages e1003379  
  Keywords African Americans/genetics; Apolipoproteins A/*genetics; Cholesterol, HDL/blood/genetics; Cholesterol, LDL/blood/genetics; European Continental Ancestry Group/genetics; *Genome-Wide Association Study; Humans; Lipoproteins, HDL/blood/genetics; Lipoproteins, LDL/blood/genetics; Proprotein Convertases/*genetics; Serine Endopeptidases/*genetics; Triglycerides/blood/genetics  
  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 x 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.  
  Address Department of Genetics, University of North Carolina, Chapel Hill, North Carolina, United States of America  
  Corporate Author Thesis  
  Publisher Place of Publication Editor  
  Language English Summary Language Original Title  
  Series Editor Series Title Abbreviated Series Title  
  Series Volume Series Issue Edition  
  ISSN 1553-7390 ISBN Medium  
  Area Expedition Conference  
  Notes PMID:23555291; PMC3605054 Approved no  
  Call Number HUNT @ maria.stuifbergen @ Serial 1385  
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