3 years ago

Exome chip meta-analysis identifies novel loci and East Asian–specific coding variants that contribute to lipid levels and coronary artery disease

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

Publisher URL: https://www.nature.com/articles/ng.3978

DOI: 10.1038/ng.3978

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