Common variants at CDKAL1 and KLF9 are associated with body mass index in east Asian populations

被引：200

作者：

Okada, Yukinori ^{[1
,2
]}

Kubo, Michiaki ^{[3
]}

Ohmiya, Hiroko ^{[1
]}

Takahashi, Atsushi ^{[1
]}

Kumasaka, Natsuhiko ^{[1
]}

Hosono, Naoya ^{[3
]}

Maeda, Shiro ^{[4
]}

Wen, Wanqing ^{[5
,6
]}

Dorajoo, Rajkumar ^{[7
,8
]}

Go, Min Jin ^{[9
]}

Zheng, Wei ^{[5
,6
]}

Kato, Norihiro ^{[10
]}

Wu, Jer-Yuarn ^{[11
,12
]}

Lu, Qi ^{[13
]}

Tsunoda, Tatsuhiko ^{[14
]}

Yamamoto, Kazuhiko ^{[2
]}

Nakamura, Yusuke ^{[15
]}

Kamatani, Naoyuki ^{[1
]}

Tanaka, Toshihiro ^{[16
]}

机构：

[1] RIKEN, CGM, Lab Stat Anal, Yokohama, Kanagawa, Japan

[2] Univ Tokyo, Grad Sch Med, Dept Allergy & Rheumatol, Tokyo, Japan

[3] RIKEN, CGM, Lab Genotyping Dev, Yokohama, Kanagawa, Japan

[4] RIKEN, CGM, Lab Endocrinol & Metab, Yokohama, Kanagawa, Japan

[5] Vanderbilt Univ, Dept Med, Div Epidemiol, Vanderbilt Ctr Epidemiol, Nashville, TN USA

[6] Vanderbilt Univ, Vanderbilt Ingram Canc Ctr, Nashville, TN USA

[7] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore, Singapore

[8] Univ London Imperial Coll Sci Technol & Med, Hammersmith Hosp, Dept Genom Common Dis, Sch Publ Hlth, London, England

[9] Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do, South Korea

[10] Natl Ctr Global Hlth & Med, Dept Gene Diagnost & Therapeut, Res Inst, Tokyo, Japan

[11] Acad Sinica, Inst Biomed Sci, Taipei, Taiwan

[12] China Med Univ, Sch Chinese Med, Taichung, Taiwan

[13] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA

[14] RIKEN, CGM, Lab Med Informat, Yokohama, Kanagawa, Japan

[15] Univ Tokyo, Inst Med Sci, Ctr Human Genome, Lab Mol Med, Tokyo, Japan

[16] RIKEN, CGM, Lab Cardiovasc Dis, Yokohama, Kanagawa, Japan

来源：

NATURE GENETICS | 2012年 / 44卷 / 03期

关键词：

GENOME-WIDE ASSOCIATION; GENETIC-VARIATION; ADULT OBESITY; HHEX-IDE; WEIGHT; RISK; LOCI; HEIGHT; MC4R;

D O I：

10.1038/ng.1086

中图分类号：

Q3 [遗传学];

学科分类号：

071007 ; 090102 ;

摘要：

Obesity is a disorder with a complex genetic etiology, and its epidemic is a worldwide problem. Although multiple genetic loci associated with body mass index, the most common measure of obesity, have been identified in European populations, few studies have focused on Asian populations. Here we report a genome-wide association study and replication studies with 62,245 east Asian subjects, which identified two new body mass index-associated loci in the CDKAL1 locus at 6p22 (rs2206734, P = 1.4 x 10(-11)) and the KLF9 locus at 9q21 (rs11142387, P = 1.3 x 10(-9)), as well as several previously reported loci (the SEC16B, BDNF, FTO, MC4R and GIPR loci, P < 5.0 x 10(-8)). We subsequently performed gene-gene interaction analyses and identified an interaction (P = 2.0 x 10(-8)) between a SNP in the KLF9 locus (rs11142387) and one in the MSTN (also known as GDF8) locus at 2q32 (rs13034723). These findings should provide useful insights into the etiology of obesity.

引用

页码：302 / U105

页数：7

共 38 条

[1] Type 2 diabetes risk alleles near ADCY5, CDKAL1 and HHEX-IDE are associated with reduced birthweight
Andersson, E. A.
Pilgaard, K.
Pisinger, C.
Harder, M. N.
Grarup, N.
Faerch, K.
Poulsen, P.
Witte, D. R.
Jorgensen, T.
Vaag, A.
Hansen, T.
Pedersen, O.
[J]. DIABETOLOGIA, 2010, 53 (09) : 1908 - 1916
[2] Appropriate body-mass index for Asian populations and its implications for policy and intervention strategies
Barba, C
Cavalli-Sforza, T
Cutter, J
Darnton-Hill, I
Deurenberg, P
Deurenberg-Yap, M
Gill, T
James, P
Ko, G
Miu, AH
Kosulwat, V
Kumanyika, S
Kurpad, A
Mascie-Taylor, N
Moon, HK
Nishida, C
Noor, MI
Reddy, KS
Rush, E
Schultz, JT
Seidell, J
Stevens, J
Swinburn, B
Tan, K
Weisell, R
Wu, ZS
Yajnik, CS
Yoshiike, N
Zimmet, P
[J]. LANCET, 2004, 363 (9403) : 157 - 163
[3] An evolutionarily conserved Myostatin proximal promoter/enhancer confers basal levels of transcription and spatial specificity in vivo
Carvalho Grade, Carla Vermeulen
Salerno, Monica Senna
Schubert, Frank R.
Dietrich, Susanne
Alvares, Lucia Elvira
[J]. DEVELOPMENT GENES AND EVOLUTION, 2009, 219 (9-10) : 497 - 508
[4] Common genetic variation near MC4R is associated with waist circumference and insulin resistance
Chambers, John C.
Elliott, Paul
Zabaneh, Delilah
Zhang, Weihua
Li, Yun
Froguel, Philippe
Balding, David
Scott, James
Kooner, Jaspal S.
[J]. NATURE GENETICS, 2008, 40 (06) : 716 - 718
[5] A large-scale genome-wide association study of Asian populations uncovers genetic factors influencing eight quantitative traits
Cho, Yoon Shin
Go, Min Jin
Kim, Young Jin
Heo, Jee Yeon
Oh, Ji Hee
Ban, Hyo-Jeong
Yoon, Dankyu
Lee, Mi Hee
Kim, Dong-Joon
Park, Miey
Cha, Seung-Hun
Kim, Jun-Woo
Han, Bok-Ghee
Min, Haesook
Ahn, Younjhin
Park, Man Suk
Han, Hye Ree
Jang, Hye-Yoon
Cho, Eun Young
Lee, Jong-Eun
Cho, Nam H.
Shin, Chol
Park, Taesung
Park, Ji Wan
Lee, Jong-Keuk
Cardon, Lon
Clarke, Geraldine
McCarthy, Mark I.
Lee, Jong-Young
Lee, Jong-Koo
Oh, Bermseok
Kim, Hyung-Lae
[J]. NATURE GENETICS, 2009, 41 (05) : 527 - 534
[6] Detecting gene-gene interactions that underlie human diseases
Cordell, Heather J.
[J]. NATURE REVIEWS GENETICS, 2009, 10 (06) : 392 - 404
[7] Deurenberg P, 2002, Obes Rev, V3, P141, DOI 10.1046/j.1467-789X.2002.00065.x
[8] Genomic control for association studies
Devlin, B
Roeder, K
[J]. BIOMETRICS, 1999, 55 (04) : 997 - 1004
[9] Elkasrawy MN, 2010, J MUSCULOSKEL NEURON, V10, P56
[10] A common variant in the FTO gene is associated with body mass index and predisposes to childhood and adult obesity
Frayling, Timothy M.
Timpson, Nicholas J.
Weedon, Michael N.
Zeggini, Eleftheria
Freathy, Rachel M.
Lindgren, Cecilia M.
Perry, John R. B.
Elliott, Katherine S.
Lango, Hana
Rayner, Nigel W.
Shields, Beverley
Harries, Lorna W.
Barrett, Jeffrey C.
Ellard, Sian
Groves, Christopher J.
Knight, Bridget
Patch, Ann-Marie
Ness, Andrew R.
Ebrahim, Shah
Lawlor, Debbie A.
Ring, Susan M.
Ben-Shlomo, Yoav
Jarvelin, Marjo-Riitta
Sovio, Ulla
Bennett, Amanda J.
Melzer, David
Ferrucci, Luigi
Loos, Ruth J. F.
Barroso, Ines
Wareham, Nicholas J.
Karpe, Fredrik
Owen, Katharine R.
Cardon, Lon R.
Walker, Mark
Hitman, Graham A.
Palmer, Colin N. A.
Doney, Alex S. F.
Morris, Andrew D.
Smith, George Davey
Hattersley, Andrew T.
McCarthy, Mark I.
[J]. SCIENCE, 2007, 316 (5826) : 889 - 894

← 1 2 3 4 →