Trans-ethnic fine-mapping of lipid loci identifies population-specific signals and allelic heterogeneity that increases the trait variance explained

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...

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Veröffentlicht in:PLoS genetics 2013-03, Vol.9 (3), p.e1003379-e1003379
Hauptverfasser: Wu, Ying, Waite, Lindsay L, Jackson, Anne U, Sheu, Wayne H-H, Buyske, Steven, Absher, Devin, Arnett, Donna K, Boerwinkle, Eric, Bonnycastle, Lori L, Carty, Cara L, Cheng, Iona, Cochran, Barbara, Croteau-Chonka, Damien C, Dumitrescu, Logan, Eaton, Charles B, Franceschini, Nora, Guo, Xiuqing, Henderson, Brian E, Hindorff, Lucia A, Kim, Eric, Kinnunen, Leena, Komulainen, Pirjo, Lee, Wen-Jane, Le Marchand, Loic, Lin, Yi, Lindström, Jaana, Lingaas-Holmen, Oddgeir, Mitchell, Sabrina L, Narisu, Narisu, Robinson, Jennifer G, Schumacher, Fred, Stančáková, Alena, Sundvall, Jouko, Sung, Yun-Ju, Swift, Amy J, Wang, Wen-Chang, Wilkens, Lynne, Wilsgaard, Tom, Young, Alicia M, Adair, Linda S, Ballantyne, Christie M, Bůžková, Petra, Chakravarti, Aravinda, Collins, Francis S, Duggan, David, Feranil, Alan B, Ho, Low-Tone, Hung, Yi-Jen, Hunt, Steven C, Hveem, Kristian, Juang, Jyh-Ming J, Kesäniemi, Antero Y, Kuusisto, Johanna, Laakso, Markku, Lakka, Timo A, Lee, I-Te, Leppert, Mark F, Matise, Tara C, Moilanen, Leena, Njølstad, Inger, Peters, Ulrike, Quertermous, Thomas, Rauramaa, Rainer, Rotter, Jerome I, Saramies, Jouko, Tuomilehto, Jaakko, Uusitupa, Matti, Wang, Tzung-Dau, Boehnke, Michael, Haiman, Christopher A, Chen, Yii-Der I, Kooperberg, Charles, Assimes, Themistocles L, Crawford, Dana C, Hsiung, Chao A, North, Kari E, Mohlke, Karen L
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Zusammenfassung: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
ISSN:1553-7404
1553-7390
1553-7404
DOI:10.1371/journal.pgen.1003379