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

Meian He, Min Xu, Ben Zhang, Jun Liang, Peng Chen, Jong Young Lee, Todd A. Johnson, Huaixing Li, Xiaobo Yang, Juncheng Dai, Liming Liang, Lixuan Gui, Qibin Qi, Jinyan Huang, Yanping Li, Linda S. Adair, Tin Aung, Qiuyin Cai, Ching Yu Cheng, Myeong Chan Cho & 70 others Yoon Shin Cho, Minjie Chu, Bin Cui, Yu Tang Gao, Min Jin Go, Dongfeng Gu, Weiqiong Gu, Huan Guo, Yongchen Hao, Jie Hong, Zhibin Hu, Yanling Hu, Jianfeng Huang, Joo Yeon Hwang, Mohammad Kamran Ikram, Guangfu Jin, Dae Hee Kang, Chiea Chuen Khor, Bong Jo Kim, Hung Tae Kim, Michiaki Kubo, Jeannette Lee, Juyoung Lee, Nanette R. Lee, Ruoying Li, Jun Li, JianJun Liu, Jirong Longe, Wei Lu, Xiangfeng Lu, Xiaoping Miao, Yukinori Okada, Rick Twee Hee Ong, Gaokun Qiu, Mark Seielstad, Xueling Sim, Huaidong Song, Fumihiko Takeuchi, Toshihiro Tanaka, Phil R. Taylor, Laiyuan Wang, Weiqing Wang, Yiqin Wang, Chen Wu, Ying Wu, Yong Bing Xiang, Ken Yamamoto, Handong Yang, Ming Liao, Mitsuhiro Yokota, Terri Young, Xiaomin Zhang, Norihiro Kato, Qing K. Wang, Wei Zheng, Frank B. Hu, Dongxin Lin, Hongbing Shen, Yik Ying Teo, Zengnan Mo, Tien Yin Wong, Xu Lin, Karen L. Mohlke, Guang Ning, Tatsuhiko Tsunoda, Bok Ghee Han, Xiao Ou Shu, E. Shyong Tai, Tangchun Wu, Lu Qi

Research output: Contribution to journalArticle

39 Citations (Scopus)

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<sup>-8</sup>, 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 languageEnglish (US)
Article numberddu583
Pages (from-to)1791-1800
Number of pages10
JournalHuman Molecular Genetics
Volume24
Issue number6
DOIs
StatePublished - 2015
Externally publishedYes

Fingerprint

Genome-Wide Association Study
Meta-Analysis
Protein Tyrosine Phosphatases
Genetic Loci
Far East
Linkage Disequilibrium
Medical Genetics
Gene Frequency
Single Nucleotide Polymorphism
Population

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)
  • Molecular Biology

Cite this

He, M., Xu, M., Zhang, B., Liang, J., Chen, P., Lee, J. Y., ... Qi, L. (2015). Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. Human Molecular Genetics, 24(6), 1791-1800. [ddu583]. https://doi.org/10.1093/hmg/ddu583

Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. / He, Meian; Xu, Min; Zhang, Ben; Liang, Jun; Chen, Peng; Lee, Jong Young; Johnson, Todd A.; Li, Huaixing; Yang, Xiaobo; Dai, Juncheng; Liang, Liming; Gui, Lixuan; Qi, Qibin; Huang, Jinyan; Li, Yanping; Adair, Linda S.; Aung, Tin; Cai, Qiuyin; Cheng, Ching Yu; Cho, Myeong Chan; Cho, Yoon Shin; Chu, Minjie; Cui, Bin; Gao, Yu Tang; Go, Min Jin; Gu, Dongfeng; Gu, Weiqiong; Guo, Huan; Hao, Yongchen; Hong, Jie; Hu, Zhibin; Hu, Yanling; Huang, Jianfeng; Hwang, Joo Yeon; Ikram, Mohammad Kamran; Jin, Guangfu; Kang, Dae Hee; Khor, Chiea Chuen; Kim, Bong Jo; Kim, Hung Tae; Kubo, Michiaki; Lee, Jeannette; Lee, Juyoung; Lee, Nanette R.; Li, Ruoying; Li, Jun; Liu, JianJun; Longe, Jirong; Lu, Wei; Lu, Xiangfeng; Miao, Xiaoping; Okada, Yukinori; Ong, Rick Twee Hee; Qiu, Gaokun; Seielstad, Mark; Sim, Xueling; Song, Huaidong; Takeuchi, Fumihiko; Tanaka, Toshihiro; Taylor, Phil R.; Wang, Laiyuan; Wang, Weiqing; Wang, Yiqin; Wu, Chen; Wu, Ying; Xiang, Yong Bing; Yamamoto, Ken; Yang, Handong; Liao, Ming; Yokota, Mitsuhiro; Young, Terri; Zhang, Xiaomin; Kato, Norihiro; Wang, Qing K.; Zheng, Wei; Hu, Frank B.; Lin, Dongxin; Shen, Hongbing; Teo, Yik Ying; Mo, Zengnan; Wong, Tien Yin; Lin, Xu; Mohlke, Karen L.; Ning, Guang; Tsunoda, Tatsuhiko; Han, Bok Ghee; Shu, Xiao Ou; Tai, E. Shyong; Wu, Tangchun; Qi, Lu.

In: Human Molecular Genetics, Vol. 24, No. 6, ddu583, 2015, p. 1791-1800.

Research output: Contribution to journalArticle

He, M, Xu, M, Zhang, B, Liang, J, Chen, P, Lee, JY, Johnson, TA, Li, H, Yang, X, Dai, J, Liang, L, Gui, L, Qi, Q, Huang, J, Li, Y, Adair, LS, Aung, T, Cai, Q, Cheng, CY, Cho, MC, Cho, YS, Chu, M, Cui, B, Gao, YT, Go, MJ, Gu, D, Gu, W, Guo, H, Hao, Y, Hong, J, Hu, Z, Hu, Y, Huang, J, Hwang, JY, Ikram, MK, Jin, G, Kang, DH, Khor, CC, Kim, BJ, Kim, HT, Kubo, M, Lee, J, Lee, J, Lee, NR, Li, R, Li, J, Liu, J, Longe, J, Lu, W, Lu, X, Miao, X, Okada, Y, Ong, RTH, Qiu, G, Seielstad, M, Sim, X, Song, H, Takeuchi, F, Tanaka, T, Taylor, PR, Wang, L, Wang, W, Wang, Y, Wu, C, Wu, Y, Xiang, YB, Yamamoto, K, Yang, H, Liao, M, Yokota, M, Young, T, Zhang, X, Kato, N, Wang, QK, Zheng, W, Hu, FB, Lin, D, Shen, H, Teo, YY, Mo, Z, Wong, TY, Lin, X, Mohlke, KL, Ning, G, Tsunoda, T, Han, BG, Shu, XO, Tai, ES, Wu, T & Qi, L 2015, 'Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci', Human Molecular Genetics, vol. 24, no. 6, ddu583, pp. 1791-1800. https://doi.org/10.1093/hmg/ddu583
He, Meian ; Xu, Min ; Zhang, Ben ; Liang, Jun ; Chen, Peng ; Lee, Jong Young ; Johnson, Todd A. ; Li, Huaixing ; Yang, Xiaobo ; Dai, Juncheng ; Liang, Liming ; Gui, Lixuan ; Qi, Qibin ; Huang, Jinyan ; Li, Yanping ; Adair, Linda S. ; Aung, Tin ; Cai, Qiuyin ; Cheng, Ching Yu ; Cho, Myeong Chan ; Cho, Yoon Shin ; Chu, Minjie ; Cui, Bin ; Gao, Yu Tang ; Go, Min Jin ; Gu, Dongfeng ; Gu, Weiqiong ; Guo, Huan ; Hao, Yongchen ; Hong, Jie ; Hu, Zhibin ; Hu, Yanling ; Huang, Jianfeng ; Hwang, Joo Yeon ; Ikram, Mohammad Kamran ; Jin, Guangfu ; Kang, Dae Hee ; Khor, Chiea Chuen ; Kim, Bong Jo ; Kim, Hung Tae ; Kubo, Michiaki ; Lee, Jeannette ; Lee, Juyoung ; Lee, Nanette R. ; Li, Ruoying ; Li, Jun ; Liu, JianJun ; Longe, Jirong ; Lu, Wei ; Lu, Xiangfeng ; Miao, Xiaoping ; Okada, Yukinori ; Ong, Rick Twee Hee ; Qiu, Gaokun ; Seielstad, Mark ; Sim, Xueling ; Song, Huaidong ; Takeuchi, Fumihiko ; Tanaka, Toshihiro ; Taylor, Phil R. ; Wang, Laiyuan ; Wang, Weiqing ; Wang, Yiqin ; Wu, Chen ; Wu, Ying ; Xiang, Yong Bing ; Yamamoto, Ken ; Yang, Handong ; Liao, Ming ; Yokota, Mitsuhiro ; Young, Terri ; Zhang, Xiaomin ; Kato, Norihiro ; Wang, Qing K. ; Zheng, Wei ; Hu, Frank B. ; Lin, Dongxin ; Shen, Hongbing ; Teo, Yik Ying ; Mo, Zengnan ; Wong, Tien Yin ; Lin, Xu ; Mohlke, Karen L. ; Ning, Guang ; Tsunoda, Tatsuhiko ; Han, Bok Ghee ; Shu, Xiao Ou ; Tai, E. Shyong ; Wu, Tangchun ; Qi, Lu. / Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci. In: Human Molecular Genetics. 2015 ; Vol. 24, No. 6. pp. 1791-1800.
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title = "Meta-analysis of genome-wide association studies of adult height in East Asians identifies 17 novel loci",
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.",
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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, JianJun

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

PY - 2015

Y1 - 2015

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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