Exome-wide Association Analysis Reveals Novel Coding Sequence Variants Associated with Lipid Traits in Chinese

Overview

Journal Nat Commun

Specialty Biology

Date 2015 Dec 23

PMID 26690388

Citations 54

Authors

Clara S Tang

He Zhang

Chloe Y Y Cheung

Ming Xu

Jenny C Y Ho

Wei Zhou

Stacey S Cherny

Yan Zhang

Oddgeir Holmen

Ka-Wing Au

Haiyi Yu

Lin Xu

Jia Jia

Robert M Porsch

Lijie Sun

Weixian Xu

Huiping Zheng

Lai-Yung Wong

Yiming Mu

Jingtao Dou

Carol H Y Fong

Shuyu Wang

Xueyu Hong

Liguang Dong

Yanhua Liao

Jiansong Wang

Levina S M Lam

Xi Su

Hua Yan

Min-Lee Yang

Jin Chen

Chung-Wah Siu

Gaoqiang Xie

Yu-Cho Woo

Yangfeng Wu

Kathryn C B Tan

Kristian Hveem

Bernard M Y Cheung

Sebastian Zollner

Aimin Xu

Y Eugene Chen

Chao Qiang Jiang

Youyi Zhang

Tai-Hing Lam

Santhi K Ganesh

Yong Huo

Pak C Sham

Karen S L Lam

Cristen J Willer

Hung-Fat Tse

Wei Gao

Affiliations

Soon will be listed here.

Abstract

Blood lipids are important risk factors for coronary artery disease (CAD). Here we perform an exome-wide association study by genotyping 12,685 Chinese, using a custom Illumina HumanExome BeadChip, to identify additional loci influencing lipid levels. Single-variant association analysis on 65,671 single nucleotide polymorphisms reveals 19 loci associated with lipids at exome-wide significance (P<2.69 × 10(-7)), including three Asian-specific coding variants in known genes (CETP p.Asp459Gly, PCSK9 p.Arg93Cys and LDLR p.Arg257Trp). Furthermore, missense variants at two novel loci-PNPLA3 p.Ile148Met and PKD1L3 p.Thr429Ser-also influence levels of triglycerides and low-density lipoprotein cholesterol, respectively. Another novel gene, TEAD2, is found to be associated with high-density lipoprotein cholesterol through gene-based association analysis. Most of these newly identified coding variants show suggestive association (P<0.05) with CAD. These findings demonstrate that exome-wide genotyping on samples of non-European ancestry can identify additional population-specific possible causal variants, shedding light on novel lipid biology and CAD.

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