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

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

Research output: Contribution to journalArticle

38 Scopus citations

Abstract

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.

Original languageEnglish (US)
Pages (from-to)1722-1730
Number of pages9
JournalNature Genetics
Volume49
Issue number12
DOIs
StatePublished - Dec 1 2017

All Science Journal Classification (ASJC) codes

  • Genetics

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    Lu, X., Peloso, G. M., Liu, D. J., Wu, Y., Zhang, H., Zhou, W., Li, J., Tang, C. S. M., Dorajoo, R., Li, H., Long, J., Guo, X., Xu, M., Spracklen, C. N., Chen, Y., Liu, X., Zhang, Y., Khor, C. C., Liu, J., ... Willer, C. 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), 1722-1730. https://doi.org/10.1038/ng.3978