A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits

被引：777

作者：

Cho, Yoon Shin ^{[1
]}

Go, Min Jin ^{[1
]}

Kim, Young Jin ^{[1
]}

Heo, Jee Yeon ^{[1
]}

Oh, Ji Hee ^{[1
]}

Ban, Hyo-Jeong ^{[1
]}

Yoon, Dankyu ^{[2
]}

Lee, Mi Hee ^{[1
]}

Kim, Dong-Joon ^{[1
]}

Park, Miey ^{[1
]}

Cha, Seung-Hun ^{[1
]}

Kim, Jun-Woo ^{[1
]}

Han, Bok-Ghee ^{[1
]}

Min, Haesook ^{[1
]}

Ahn, Younjhin ^{[1
]}

Park, Man Suk ^{[1
]}

Han, Hye Ree ^{[1
,3
]}

Jang, Hye-Yoon ^{[3
]}

Cho, Eun Young ^{[3
]}

Lee, Jong-Eun

Cho, Nam H. ^{[4
]}

Shin, Chol ^{[5
]}

Park, Taesung ^{[2
,6
]}

Park, Ji Wan ^{[7
]}

Lee, Jong-Keuk ^{[1
,8
]}

Cardon, Lon ^{[9
]}

Clarke, Geraldine ^{[10
]}

McCarthy, Mark I. ^{[10
,11
]}

Lee, Jong-Young

Lee, Jong-Koo ^{[12
]}

Oh, Bermseok ^{[1
,13
]}

Kim, Hyung-Lae ^{[1
]}

机构：

[1] Natl Inst Hlth, Ctr Genome Sci, Seoul, South Korea

[2] Seoul Natl Univ, Interdisciplinary Program Bioinformat, Seoul, South Korea

[3] DNA Link, Seoul, South Korea

[4] Ajou Univ, Sch Med, Dept Prevent Med, Suwon 441749, South Korea

[5] Korea Univ, Ansan Hosp, Dept Internal Med, Div Pulm & Crit Care Med, Ansan, South Korea

[6] Seoul Natl Univ, Coll Nat Sci, Dept Stat, Seoul 151742, South Korea

[7] Hallym Univ, Coll Med, Dept Med Genet, Chunchon, South Korea

[8] Univ Ulsan, Coll Med, Asan Inst Life Sci, Seoul, South Korea

[9] GlaxoSmithKline Inc, Philadelphia, PA USA

[10] Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford, England

[11] Churchill Hosp, Oxford Ctr Diabet Endocrinol & Metab, Oxford OX3 7LJ, England

[12] Korea Ctr Dis Control & Prevent, Seoul, South Korea

[13] Kyung Hee Univ, Sch Med, Dept Biomed Engn, Seoul, South Korea

来源：

NATURE GENETICS | 2009年 / 41卷 / 05期

关键词：

PLASMA-MEMBRANE; CELLS; OBESITY; HEIGHT; MASS; EXPRESSION; VARIANTS; PROTEINS; ARRAYS; LOCI;

D O I：

10.1038/ng.357

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

To identify genetic factors influencing quantitative traits of biomedical importance, we conducted a genome-wide association study in 8,842 samples from population-based cohorts recruited in Korea. For height and body mass index, most variants detected overlapped those reported in European samples. For the other traits examined, replication of promising GWAS signals in 7,861 independent Korean samples identified six previously unknown loci. For pulse rate, signals reaching genome-wide significance mapped to chromosomes 1q32 (rs12731740, P = 2.9 x 10(-9)) and 6q22 (rs12110693, P = 1.6 x 10(-9)), with the latter similar to 400 kb from the coding sequence of GJA1. For systolic blood pressure, the most compelling association involved chromosome 12q21 and variants near the ATP2B1 gene (rs17249754, P = 1.3 x 10(-7)). For waist-hip ratio, variants on chromosome 12q24 (rs2074356, P = 7.8 x 10(-12)) showed convincing associations, although no regional transcript has strong biological candidacy. Finally, we identified two loci influencing bone mineral density at multiple sites. On chromosome 7q31, rs7776725 (within the FAM3C gene) was associated with bone density at the radius (P = 1.0 x 10(-11)), tibia (P = 1.6 x 10(-6)) and heel (P = 1.9 x 10(-10)). On chromosome 7p14, rs1721400 (mapping close to SFRP4, a frizzled protein gene) showed consistent associations at the same three sites (P = 2.2 x 10(-3), P = 1.4 x 10(-7) and P = 6.0 x 10(-4), respectively). This large-scale GWA analysis of well-characterized Korean population-based samples highlights previously unknown biological pathways.

引用

页码：527 / 534

页数：8

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