Gaoqiang Xie1, Phyo Kyaw Myint2, Deepak Voora3, Daniel T Laskowitz4, Ping Shi5, Fuxiu Ren5, Hao Wang6, Ying Yang7, Yong Huo7, Wei Gao8, Yangfeng Wu9. 1. Peking University Clinical Research Institute, Beijing, China. Electronic address: gxie@bjmu.edu.cn. 2. 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. 3. Duke University Genome Research Institute, USA. 4. Department of Neurology, Duke University Medicine Center, Durham, NC, USA. 5. Shijingshan Center for Disease Control and Prevention, Beijing, China. 6. 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. 7. Department of Cardiology, Peking University First Hospital, Beijing, China. 8. Department of Cardiology, Peking University Third Hospital, Beijing, China; Key Laboratory of Molecular Cardiovascular Sciences, Ministry of Education, Beijing, China. 9. 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.
Abstract
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)). CONCLUSION: 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.
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)). CONCLUSION: 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.
Authors: Allison L Kuipers; Mary K Wojczynski; Emma Barinas-Mitchell; Ryan L Minster; Lihua Wang; Mary F Feitosa; Alexander Kulminski; Bharat Thyagarajan; Joseph H Lee; Michael A Province; Anne B Newman; Joseph M Zmuda Journal: Atherosclerosis Date: 2019-10-10 Impact factor: 5.162
Authors: Maria S Nazarenko; Aleksei A Sleptcov; Igor N Lebedev; Nikolay A Skryabin; Anton V Markov; Maria V Golubenko; Iuliia A Koroleva; Anton N Kazancev; Olga L Barbarash; Valery P Puzyrev Journal: Sci Rep Date: 2017-01-25 Impact factor: 4.379
Authors: Ge Zhang; Bjarke Feenstra; Jonas Bacelis; Xueping Liu; Lisa M Muglia; Julius Juodakis; Daniel E Miller; Nadia Litterman; Pan-Pan Jiang; Laura Russell; David A Hinds; Youna Hu; Matthew T Weirauch; Xiaoting Chen; Arun R Chavan; Günter P Wagner; Mihaela Pavličev; Mauris C Nnamani; Jamie Maziarz; Minna K Karjalainen; Mika Rämet; Verena Sengpiel; Frank Geller; Heather A Boyd; Aarno Palotie; Allison Momany; Bruce Bedell; Kelli K Ryckman; Johanna M Huusko; Carmy R Forney; Leah C Kottyan; Mikko Hallman; Kari Teramo; Ellen A Nohr; George Davey Smith; Mads Melbye; Bo Jacobsson; Louis J Muglia Journal: N Engl J Med Date: 2017-09-06 Impact factor: 91.245