Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci

被引:77
作者
He, Meian [1 ]
Xu, Min [2 ,3 ]
Zhang, Ben [5 ]
Liang, Jun [6 ]
Chen, Peng [7 ]
Lee, Jong-Young [14 ]
Johnson, Todd A. [15 ]
Li, Huaixing [19 ]
Yang, Xiaobo [20 ,21 ,23 ]
Dai, Juncheng [24 ]
Liang, Liming [2 ]
Gui, Lixuan [1 ]
Qi, Qibin [2 ]
Huang, Jinyan [2 ]
Li, Yanping [2 ]
Adair, Linda S. [25 ]
Aung, Tin [27 ]
Cai, Qiuyin [5 ]
Cheng, Ching-Yu [7 ,8 ,27 ,28 ]
Cho, Myeong-Chan [14 ]
Cho, Yoon Shin [14 ]
Chu, Minjie [24 ]
Cui, Bin [3 ]
Gao, Yu-Tang [29 ]
Go, Min Jin [14 ]
Gu, Dongfeng [30 ]
Gu, Weiqiong [3 ]
Guo, Huan [1 ]
Hao, Yongchen [30 ]
Hong, Jie [3 ]
Hu, Zhibin [24 ]
Hu, Yanling [22 ]
Huang, Jianfeng [30 ]
Hwang, Joo-Yeon [14 ]
Ikram, Mohammad Kamran [7 ,8 ,27 ,33 ,34 ]
Jin, Guangfu [24 ]
Kang, Dae-Hee [35 ]
Khor, Chiea Chuen [7 ,8 ,9 ,36 ]
Kim, Bong-Jo [14 ]
Kim, Hung Tae [14 ]
Kubo, Michiaki [16 ]
Lee, Jeannette [7 ]
Lee, Juyoung [14 ]
Lee, Nanette R. [37 ]
Li, Ruoying [10 ]
Li, Jun [1 ]
Liu, JianJun [7 ,36 ]
Longe, Jirong [5 ]
Lu, Wei [38 ]
Lu, Xiangfeng [30 ]
机构
[1] Huazhong Univ Sci & Technol, Tongji Med Coll, Sch Publ Hlth, MOE Key Lab Environm & Hlth, Wuhan 430030, Hubei, Peoples R China
[2] Harvard Univ, Sch Publ Hlth, Dept Nutr, Boston, MA 02115 USA
[3] Shanghai Jiao Tong Univ, Shanghai Inst Endocrine & Metab Dis,Minist Hlth, Shanghai Clin Ctr Endocrine & Metab Dis,Sch Med,R, Key Lab Endocrine & Metab Dis,Dept Endocrinol & M, Shanghai 200025, Peoples R China
[4] Shanghai Jiao Tong Univ, State Key Lab Med Genom, Shanghai Inst Endocrine & Metab Dis, Mol Med Ctr,Ruijin Hosp,Sch Med, Shanghai 200025, Peoples R China
[5] Vanderbilt Univ, Sch Med, Vanderbilt Epidemiol Ctr, Div Epidemiol,Dept Med, Nashville, TN 37232 USA
[6] Southeast Univ, Affiliated Hosp, Cent Hosp Xuzhou, Dept Endocrinol, Xuzhou 221009, Jiangsu, Peoples R China
[7] Natl Univ Singapore, Saw Swee Hock Sch Publ Hlth, Singapore 119077, Singapore
[8] Natl Univ Singapore, Dept Ophthalmol, Singapore 119077, Singapore
[9] Natl Univ Singapore, Dept Paediat, Natl Univ Hlth Syst, Singapore 119077, Singapore
[10] Natl Univ Singapore, Dept Med, Yong Loo Lin Sch Med, Singapore 119077, Singapore
[11] Natl Univ Singapore, NUS Grad Sch Integrat Sci & Engn, Singapore 119077, Singapore
[12] Natl Univ Singapore, Inst Life Sci, Singapore 119077, Singapore
[13] Natl Univ Singapore, Dept Stat & Appl Probabil, Singapore 119077, Singapore
[14] Osong Hlth Technol Adm Complex, Natl Inst Hlth, Ctr Genome Sci, Chungcheongbuk Do 363700, South Korea
[15] RIKEN Ctr Genom Med, Lab Med Informat, Yokohama, Kanagawa 2300045, Japan
[16] RIKEN Ctr Genom Med, Lab Genotyping Dev, Yokohama, Kanagawa 2300045, Japan
[17] RIKEN Ctr Genom Med, Lab Stat Anal, Yokohama, Kanagawa 2300045, Japan
[18] RIKEN Ctr Genom Med, Lab Cardiovasc Dis, Yokohama, Kanagawa 2300045, Japan
[19] Chinese Acad Sci, Shanghai Inst Biol Sci, Key Lab Nutr & Metab, Inst Nutr Sci, Shanghai 200031, Peoples R China
[20] Guangxi Med Univ, Inst Urol & Nephrol, Affiliated Hosp 1, Nanning 530021, Guangxi, Peoples R China
[21] Guangxi Med Univ, Ctr Genom & Personalized Med, Nanning 530021, Guangxi, Peoples R China
[22] Guangxi Med Univ, Med Sci Res Ctr, Nanning 530021, Guangxi, Peoples R China
[23] Guangxi Med Univ, Dept Environm & Occupat Hlth, Sch Publ Hlth, Nanning 530021, Guangxi, Peoples R China
[24] Nanjing Med Univ, Dept Epidemiol & Biostat, Sch Publ Hlth, Nanjing 210029, Jiangsu, Peoples R China
[25] Univ N Carolina, Dept Nutr, Chapel Hill, NC 27599 USA
[26] Univ N Carolina, Dept Genet, Chapel Hill, NC 27599 USA
[27] Singapore Natl Eye Ctr, Singapore Eye Res Inst, Singapore 168751, Singapore
[28] Duke Natl Univ Singapore, Grad Sch Med, Singapore 169857, Singapore
[29] Shanghai Jiao Tong Univ, Sch Med, Shanghai Canc Inst, Dept Epidemiol, Shanghai 200025, Peoples R China
[30] Chinese Acad Med Sci, State Key Lab Cardiovasc Dis, Dept Evidence Based Med, Fuwai Hosp,Natl Ctr Cardiovasc Dis, Beijing 100730, Peoples R China
[31] Chinese Acad Med Sci, State Key Lab Mol Oncol, Canc Inst & Hosp, Beijing 100730, Peoples R China
[32] Peking Union Med Coll, Beijing 100730, Peoples R China
[33] Erasmus MC, Dept Ophthalmol, NL-3015 Rotterdam, Netherlands
[34] Natl Univ Hlth Syst, Memory Aging & Cognit Ctr, Singapore 119228, Singapore
[35] Seoul Natl Univ, Coll Med, Dept Prevent Med, Seoul 110799, South Korea
[36] Agcy Sci Technol & Res, Genome Inst Singapore, Singapore 138672, Singapore
[37] Univ San Carlos, Off Populat Studies Fdn, Cebu 6000, Philippines
[38] Shanghai Municipal Ctr Dis Control & Prevent, Shanghai 200336, Peoples R China
[39] Univ Michigan, Dept Biostat, Ann Arbor, MI 48109 USA
[40] Univ Michigan, Ctr Stat Genet, Ann Arbor, MI 48109 USA
[41] Natl Ctr Global Hlth & Med, Res Inst, Dept Gene Diagnost & Therapeut, Tokyo 1628655, Japan
[42] NCI, Div Canc Epidemiol & Genet, Genet Epidemiol Branch, Bethesda, MD 20892 USA
[43] Kyushu Univ, Dept Mol Genet, Med Inst Bioregulat, Fukuoka 8128582, Japan
[44] Dongfeng Motor Corp, Dongfeng Cent Hosp, Dept Cardiol, Shiyan 442008, Hubei, Peoples R China
[45] Hubei Univ Med, Shiyan 442008, Hubei, Peoples R China
[46] Aichi Gakuin Univ, Sch Dent, Dept Genome Sci, Nagoya, Aichi 4648650, Japan
[47] Duke Univ, Med Ctr, Duke Eye Ctr, Durham, NC 27710 USA
[48] Huazhong Univ Sci & Technol, Key Lab Mol Biophys, Minist Educ, Coll Life Sci & Technol,Cardio X Inst, Wuhan 430074, Hubei, Peoples R China
[49] Huazhong Univ Sci & Technol, Ctr Human Genome Res, Wuhan 430074, Hubei, Peoples R China
基金
美国国家卫生研究院; 新加坡国家研究基金会; 中国国家自然科学基金; 英国医学研究理事会;
关键词
BIOLOGICAL PATHWAYS; GENETIC-VARIANTS; RISK; IMPUTATION; MUTATIONS; PTPN11; CANCER; COHORT; IGF1;
D O I
10.1093/hmg/ddu583
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Human height is associated with risk of multiple diseases and is profoundly determined by an individual's genetic makeup and shows a high degree of ethnic heterogeneity. Large-scale genome-wide association (GWA) analyses of adult height in Europeans have identified nearly 180 genetic loci. A recent study showed high replicability of results from Europeans-based GWA studies in Asians; however, population-specific loci may exist due to distinct linkage disequilibrium patterns. We carried out a GWA meta-analysis in 93 926 individuals from East Asia. We identified 98 loci, including 17 novel and 81 previously reported loci, associated with height at P<5x10(-8), together explaining 8.89% of phenotypic variance. Among the newly identified variants, 10 are commonly distributed (minor allele frequency, MAF > 5%) in Europeans, with comparable frequencies with in Asians, and 7single-nucleotide polymorphisms are with low frequency (MAF <5%) in Europeans. In addition, our data suggest that novel biological pathway such as the protein tyrosine phosphatase family is involved in regulation of height. The findings from this study considerably expand our knowledge of the genetic architecture of human height in Asians.
引用
收藏
页码:1791 / 1800
页数:10
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