Abstract
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 < 5 × 10-8, 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 7 single-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.
Original language | English (US) |
---|---|
Pages (from-to) | 1791-1800 |
Number of pages | 10 |
Journal | Human molecular genetics |
Volume | 24 |
Issue number | 6 |
DOIs | |
State | Published - Mar 15 2015 |
Externally published | Yes |
ASJC Scopus subject areas
- Molecular Biology
- Genetics
- Genetics(clinical)
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In: Human molecular genetics, Vol. 24, No. 6, 15.03.2015, p. 1791-1800.
Research output: Contribution to journal › Article › peer-review
}
TY - JOUR
T1 - Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci
AU - He, Meian
AU - Xu, Min
AU - Zhang, Ben
AU - Liang, Jun
AU - Chen, Peng
AU - Lee, Jong Young
AU - Johnson, Todd A.
AU - Li, Huaixing
AU - Yang, Xiaobo
AU - Dai, Juncheng
AU - Liang, Liming
AU - Gui, Lixuan
AU - Qi, Qibin
AU - Huang, Jinyan
AU - Li, Yanping
AU - Adair, Linda S.
AU - Aung, Tin
AU - Cai, Qiuyin
AU - Cheng, Ching Yu
AU - Cho, Myeong Chan
AU - Cho, Yoon Shin
AU - Chu, Minjie
AU - Cui, Bin
AU - Gao, Yu Tang
AU - Go, Min Jin
AU - Gu, Dongfeng
AU - Gu, Weiqiong
AU - Guo, Huan
AU - Hao, Yongchen
AU - Hong, Jie
AU - Hu, Zhibin
AU - Hu, Yanling
AU - Huang, Jianfeng
AU - Hwang, Joo Yeon
AU - Ikram, Mohammad Kamran
AU - Jin, Guangfu
AU - Kang, Dae Hee
AU - Khor, Chiea Chuen
AU - Kim, Bong Jo
AU - Kim, Hung Tae
AU - Kubo, Michiaki
AU - Lee, Jeannette
AU - Lee, Juyoung
AU - Lee, Nanette R.
AU - Li, Ruoying
AU - Li, Jun
AU - Liu, Jian Jun
AU - Longe, Jirong
AU - Lu, Wei
AU - Lu, Xiangfeng
AU - Miao, Xiaoping
AU - Okada, Yukinori
AU - Ong, Rick Twee Hee
AU - Qiu, Gaokun
AU - Seielstad, Mark
AU - Sim, Xueling
AU - Song, Huaidong
AU - Takeuchi, Fumihiko
AU - Tanaka, Toshihiro
AU - Taylor, Phil R.
AU - Wang, Laiyuan
AU - Wang, Weiqing
AU - Wang, Yiqin
AU - Wu, Chen
AU - Wu, Ying
AU - Xiang, Yong Bing
AU - Yamamoto, Ken
AU - Yang, Handong
AU - Liao, Ming
AU - Yokota, Mitsuhiro
AU - Young, Terri
AU - Zhang, Xiaomin
AU - Kato, Norihiro
AU - Wang, Qing K.
AU - Zheng, Wei
AU - Hu, Frank B.
AU - Lin, Dongxin
AU - Shen, Hongbing
AU - Teo, Yik Ying
AU - Mo, Zengnan
AU - Wong, Tien Yin
AU - Lin, Xu
AU - Mohlke, Karen L.
AU - Ning, Guang
AU - Tsunoda, Tatsuhiko
AU - Han, Bok Ghee
AU - Shu, Xiao Ou
AU - Tai, E. Shyong
AU - Wu, Tangchun
AU - Qi, Lu
N1 - Funding Information: BGWAS (Beijing Genome-wide Association Studies): This work was supported by the National Basic Research Program of China (973 Plan) (2011CB503901), the High-Tech Research and Development Program of China (863 Plan) (2012AA02A516), grants (2011BAI11B03, 2011BAI09B03) from the Ministry of Science and Technology of China. CLHNS (the Cebu Longitudinal Health and Nutrition Survey): The study was supported by National Institutes of Health grants DK078150, TW05596 and HL085144 and pilot funds from RR20649, ES10126 and DK56350. We thank the Office of Population Studies Foundation research and data collection teams and the study participants who generously provided their time for this study. CRC (the Cardiometa-bolic Risk in Chinese study): This study was supported by grants from the National Heart, Lung, and Blood Institute (HL071981), the National Institute of Diabetes and Digestive and Kidney Diseases (DK091718 and DK078616), the Boston Obesity Nutrition Research Center (DK46200) and United States–Israel Binational Science Foundation Grant 2011036. FAMHES (Fang-chenggang Area Male Health and Examination Survey): This study was supported by the Guangxi Provincial Department of Finance and Education (2009GJCJ150); intramural funding from the Fudan-VARI Center for Genetic Epidemiology and Fudan University Institute of Urology to Z. Mo. HEXA (Health Examinee) shared control study, KARE (the Korea Association Resource study): The work was supported by a grant from the Korea Center for Disease Control and Prevention (4845-301, 4851-302, 4851-307), and intramural grant from the Korea National Institute of Health (2012-N73002-00). NHAPC (Nutrition and Health of Aging Population in China study): This study is supported by research grants including the National High Technology Research and Development Program (2009AA022704), Knowledge Innovation Program (KSCX2-EW-R-10), the National Natural Science Foundation of China (30930081, 81021002, 81170734) and the and National Key Basic Research Program of China (2012CB524900). NJ study (Nanjing GWA study): This work is funded by the China National High-Tech Research and Development Program Grant (2009AA022705), the National Key Basic Research Program Grant (2011CB503805), the National Natural Science Foundation of China (30730080, 30972541, 30901233 and 30872178). RJ study (RuiJin T2D study): the Key Laboratory for Endocrine and Metabolic Diseases of Ministry of Health (No.1994DP131044), the Sector Funds of Ministry of Health (No. 201002002), the National Key New Drug Creation and Manufacturing Program of Ministry of Science and Technology (No. 2012ZX09303006-001) and the National Natural Science Foundation of China (No. 81270877). SGWAS (Shanghai Genome-Wide Association Studies): The content of this paper is solely the responsibility of the authors and does not necessarily represent the official views of the funding agencies. The authors thank the study participants and research staff for their contributions and commitment to this project, Regina Courtney for DNA preparation, Jing He for data processing and analyses and Bethanie Rammer for editing and preparing the manuscript. This research was supported in part by U.S. National Institutes of Health grants R37CA070867, R01CA082729, R01CA124558, R01CA148667, and R01CA122364, as well as Ingram Professorship and Research Reward funds from the Vanderbilt University School of Medicine. Participating studies (grant support) in the Shanghai Genome Wide Association Studies are as follows: Shanghai Women’s Health Study (R37CA070867), Shanghai Men’s Health Study (R01CA82729) and Shanghai Breast and Endometrial Cancer Studies (R01CA064277 and R01CA092585). SP2 (Singapore Prospective Study Program), SCES (Singapore Chinese Eye Study) and SiMES (Singapore Malay Eye Study): the studies were supported by the Singapore Ministry of Health’s National Medical Research Council under its Individual Research Grant funding scheme, the Singapore National Research Foundation under its Clinician Scientist Award and Singapore Translational Research Investigator Award funding schemes which are administered by the Singapore Ministry of Health’s National Medical Research Council and the Singapore Biomedical Research Council (BMRC) individual research grant funding scheme. WHBJ (Wuhan-Beijing GWA study): This work was supported by grants from the National Basic Research Program grant (2011CB503800) and the Programme of Introducing Talents of Discipline to Universities to T. Wu and the Program for New Century Excellent Talents in University and the General Program of the National Natural Science Foundation of China (81172751) to M.H. Publisher Copyright: © The Author 2014. Published by Oxford University Press. All rights reserved.
PY - 2015/3/15
Y1 - 2015/3/15
N2 - 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 < 5 × 10-8, 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 7 single-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.
AB - 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 < 5 × 10-8, 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 7 single-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.
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UR - http://www.scopus.com/inward/citedby.url?scp=84936073085&partnerID=8YFLogxK
U2 - 10.1093/hmg/ddu583
DO - 10.1093/hmg/ddu583
M3 - Article
C2 - 25429064
AN - SCOPUS:84936073085
SN - 0964-6906
VL - 24
SP - 1791
EP - 1800
JO - Human Molecular Genetics
JF - Human Molecular Genetics
IS - 6
ER -