Exome Chip Meta-Analysis Identifies Novel Loci and East Asian-Specific Coding Variants That Contribute to Lipid Levels and Coronary Artery Disease

Lu, Xiangfeng; Peloso, Gina M.; Liu, Dajiang J.; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-Man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N.; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H-H; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B.; Adair, Linda S.; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; Chen, Yii-Der Ida; Shu, Xiao-Ou; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K.; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars G.; Nielsen, Jonas Bille; Tse, Hung-Fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y. Eugene; Zheng, Wei; Tai, E. Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; GLGC Consortium; Kathiresan, Sekar; Mohlke, Karen L.; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; & Willer, Cristen J. (2017). Exome Chip Meta-Analysis Identifies Novel Loci and East Asian-Specific Coding Variants That Contribute to Lipid Levels and Coronary Artery Disease. Nature Genetics, 49(12), 1722-30.

Lu, Xiangfeng; Peloso, Gina M.; Liu, Dajiang J.; Wu, Ying; Zhang, He; Zhou, Wei; Li, Jun; Tang, Clara Sze-Man; Dorajoo, Rajkumar; Li, Huaixing; Long, Jirong; Guo, Xiuqing; Xu, Ming; Spracklen, Cassandra N.; Chen, Yang; Liu, Xuezhen; Zhang, Yan; Khor, Chiea Chuen; Liu, Jianjun; Sun, Liang; Wang, Laiyuan; Gao, Yu-Tang; Hu, Yao; Yu, Kuai; Wang, Yiqin; Cheung, Chloe Yu Yan; Wang, Feijie; Huang, Jianfeng; Fan, Qiao; Cai, Qiuyin; Chen, Shufeng; Shi, Jinxiu; Yang, Xueli; Zhao, Wanting; Sheu, Wayne H-H; Cherny, Stacey Shawn; He, Meian; Feranil, Alan B.; Adair, Linda S.; Gordon-Larsen, Penny; Du, Shufa; Varma, Rohit; Chen, Yii-Der Ida; Shu, Xiao-Ou; Lam, Karen Siu Ling; Wong, Tien Yin; Ganesh, Santhi K.; Mo, Zengnan; Hveem, Kristian; Fritsche, Lars G.; Nielsen, Jonas Bille; Tse, Hung-Fat; Huo, Yong; Cheng, Ching-Yu; Chen, Y. Eugene; Zheng, Wei; Tai, E. Shyong; Gao, Wei; Lin, Xu; Huang, Wei; Abecasis, Goncalo; GLGC Consortium; Kathiresan, Sekar; Mohlke, Karen L.; Wu, Tangchun; Sham, Pak Chung; Gu, Dongfeng; & Willer, Cristen J. (2017). Exome Chip Meta-Analysis Identifies Novel Loci and East Asian-Specific Coding Variants That Contribute to Lipid Levels and Coronary Artery Disease. Nature Genetics, 49(12), 1722-30.

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Most genome-wide association studies have been of European individuals, even though most genetic variation in humans is seen only in non-European samples. To search for novel loci associated with blood lipid levels and clarify the mechanism of action at previously identified lipid loci, we used an exome array to examine protein-coding genetic variants in 47,532 East Asian individuals. We identified 255 variants at 41 loci that reached chip-wide significance, including 3 novel loci and 14 East Asian-specific coding variant associations. After a meta-analysis including >300,000 European samples, we identified an additional nine novel loci. Sixteen genes were identified by protein-altering variants in both East Asians and Europeans, and thus are likely to be functional genes. Our data demonstrate that most of the low-frequency or rare coding variants associated with lipids are population specific, and that examining genomic data across diverse ancestries may facilitate the identification of functional genes at associated loci.




JOUR



Lu, Xiangfeng
Peloso, Gina M.
Liu, Dajiang J.
Wu, Ying
Zhang, He
Zhou, Wei
Li, Jun
Tang, Clara Sze-Man
Dorajoo, Rajkumar
Li, Huaixing
Long, Jirong
Guo, Xiuqing
Xu, Ming
Spracklen, Cassandra N.
Chen, Yang
Liu, Xuezhen
Zhang, Yan
Khor, Chiea Chuen
Liu, Jianjun
Sun, Liang
Wang, Laiyuan
Gao, Yu-Tang
Hu, Yao
Yu, Kuai
Wang, Yiqin
Cheung, Chloe Yu Yan
Wang, Feijie
Huang, Jianfeng
Fan, Qiao
Cai, Qiuyin
Chen, Shufeng
Shi, Jinxiu
Yang, Xueli
Zhao, Wanting
Sheu, Wayne H-H
Cherny, Stacey Shawn
He, Meian
Feranil, Alan B.
Adair, Linda S.
Gordon-Larsen, Penny
Du, Shufa
Varma, Rohit
Chen, Yii-Der Ida
Shu, Xiao-Ou
Lam, Karen Siu Ling
Wong, Tien Yin
Ganesh, Santhi K.
Mo, Zengnan
Hveem, Kristian
Fritsche, Lars G.
Nielsen, Jonas Bille
Tse, Hung-Fat
Huo, Yong
Cheng, Ching-Yu
Chen, Y. Eugene
Zheng, Wei
Tai, E. Shyong
Gao, Wei
Lin, Xu
Huang, Wei
Abecasis, Goncalo
GLGC Consortium
Kathiresan, Sekar
Mohlke, Karen L.
Wu, Tangchun
Sham, Pak Chung
Gu, Dongfeng
Willer, Cristen J.



2017


Nature Genetics

49

12

1722-30










10657

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