Genome-wide association study on progression of carotid artery intima media thickness over 10 years in a Chinese cohort.
BACKGROUND
Carotid artery intima media thickness (IMT) in human is a marker of subclinical atherosclerosis with high heritability. Many genome-wide association studies (GWAS) were performed in European and American populations, yet discovery efforts have been limited in Asians.


OBJECTIVE
To identify the genetic determinants of 10-year progression of IMT using GWA approach in a Chinese cohort.


METHODS
Cardiovascular epidemiologic survey was carried out in 810 Chinese adults in 2012. 302,218 single-nucleotide polymorphisms (SNP) in whole genome were genotyped using gene chip and carotid IMT was measured. Most of these participants, had previous carotid IMT measurements in 2002 (n = 572), 2005 (n = 750), 2007 (n = 747), and 2010 (n = 671). General linear model (GLM) and multiple linear mixed-model (MLM) were used to assess the association between SNPs and carotid IMT.


RESULTS
The mean age (SD) of the sample was 61.3 (5.1) years; 33.6% were men. The adjusted GLM showed no SNP with significance association at genome-level (all p > 1 × 10(-7)). However, using MLM, after adjusting for age, sex, number of cigarettes smoked per day, systolic blood pressure, use of antihypertensive drugs in the past 2 weeks, serum cholesterol, body mass index, fasting glucose levels, use of insulin or hypoglycemic drugs, time of measuring IMT and its interaction with SNP, we identified two novel SNPs (rs36071027 in EBF1 gene on chromosome 5 and rs975809 close to PCDH15 gene on chromosome 10) that are significantly associated with carotid IMT at genome level (p < 1 × 10(-7)) and seven novel SNPs (rs2230307 in AGL gene on chromosome 1, rs12040273 in GALNT2 gene on chromosome 1, rs4536103 in NEUROG3 gene on chromosome 10, rs9855415 in LOC647323 gene on chromosome 3, rs2472647 in PCDHGA1 gene on chromosome 5, rs17433780 in GBP3 gene on chromosome 1, and rs7625806 in DLEC1 gene on chromosome 3) which are suggestive of significant association (p < 10(-5)).


CONCLUSIONS
The study represents the first GWAS of association between SNPs and carotid IMT in an Asian population. We identified 2 novel loci associated with carotid IMT progression over 10 years.
Peking University Clinical Research Institute, Beijing, China. Electronic address: gxie@bjmu.edu.cn.
Gaoqiang
G
Xie
Epidemiology Group, Institute of Applied Health Sciences, School of Medicine and Dentistry, University of Aberdeen, Aberdeen, Scotland, United Kingdom; Clinical Gerontology Unit, Department of Public Health and Primary Care, University of Cambridge, Cambridge, United Kingdom; Norwich Research Park Cardiovascular Research Group, Norwich Medical School, University of East Anglia, Norwich, United Kingdom; Stroke Research Group, Norfolk and Norwich University Hospital, Norwich, United Kingdom.
Phyo Kyaw
PK
Myint
Duke University Genome Research Institute, USA.
Deepak
D
Voora
Department of Neurology, Duke University Medicine Center, Durham, NC, USA.
Daniel T
DT
Laskowitz
Shijingshan Center for Disease Control and Prevention, Beijing, China.
Ping
P
Shi
Shijingshan Center for Disease Control and Prevention, Beijing, China.
Fuxiu
F
Ren
State Key Laboratory of Cardiovascular Disease, Fuwai Hospital, National Center for Cardiovascular Diseases, Chinese Academy of Medical Sciences and Peking Union Medical College, Beijing, 100037, China.
Hao
H
Wang
Department of Cardiology, Peking University First Hospital, Beijing, China.
Ying
Y
Yang
Department of Cardiology, Peking University First Hospital, Beijing, China.
Yong
Y
Huo
Department of Cardiology, Peking University Third Hospital, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China.
Wei
W
Gao
Peking University Clinical Research Institute, Beijing, China; Department of Epidemiology and Biostatistics, Peking University School of Public Health, Beijing, China. Electronic address: wuyf@bjmu.edu.cn.
Yangfeng
Y
Wu
D000368:Aged; D044466:Asian People / Q000235:genetics; D050197:Atherosclerosis / Q000097:blood* / Q000208:ethnology / Q000235:genetics*; D002339:Carotid Arteries / Q000473:pathology; D059168:Carotid Intima-Media Thickness; D002681:China; D015331:Cohort Studies; D018450:Disease Progression; D005260:Female; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D008875:Middle Aged; D020411:Oligonucleotide Array Sequence Analysis; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
Chinese; Cohort; GWAS; Intima-media thickness