title: Susceptibility loci for metabolic syndrome and metabolic components identified in Han Chinese: a multi-stage genome-wide association study.
abstract: Metabolic syndrome (MetS), a cluster of metabolic disturbances that increase the risk for cardiovascular disease and diabetes, was because of genetic susceptibility and environmental risk factors. To identify the genetic variants associated with MetS and metabolic components, we conducted a genome-wide association study followed by replications in totally 12,720 participants from the north, north-eastern and eastern China. In combined analyses, independent of the top known signal at rs651821 on APOA5, we newly identified a secondary triglyceride-associated signal at rs180326 on BUD13 (Pcombined= 2.4 × 10-8). Notably, by an integrated analysis of the genotypes and the serum levels of APOA5, BUD13 and triglyceride, we observed that BUD13 was another potential mediator, besides APOA5, of the association between rs651821 and serum triglyceride. rs671 (ALDH2), an east Asian-specific common variant, was found to be associated with MetS (Pcombined= 9.7 × 10-22) in Han Chinese. The effects of rs671 on metabolic components were more prominent in drinkers than in non-drinkers. The replicated loci provided information on the genetic basis and mechanisms of MetS and metabolic components in Han Chinese.
authors.affiliation: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Yimin
authors.initials: Y
authors.lastname: Zhu
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Dandan
authors.initials: D
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Dan
authors.initials: D
authors.lastname: Zhou
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Zhenli
authors.initials: Z
authors.lastname: Li
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Zhiqiang
authors.initials: Z
authors.lastname: Li
authors.affiliation: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China.
authors.forename: Le
authors.initials: L
authors.lastname: Fang
authors.affiliation: Department of Nutrition and Food Safety, Zhejiang University School of Public Health, Hangzhou, China.
authors.forename: Min
authors.initials: M
authors.lastname: Yang
authors.affiliation: The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Zhongyan
authors.initials: Z
authors.lastname: Shan
authors.affiliation: Department of Endocrinology, Sir Run Run Shaw Hospital Affiliated to School of Medicine, Zhejiang University, Hangzhou, Zhejiang, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Li
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Jianhua
authors.initials: J
authors.lastname: Chen
authors.affiliation: Department of Endocrinology and Metabolism, Peking University People's Hospital, Beijing, China.|Peking University Diabetes Center, Beijing, China.
authors.forename: Xianghai
authors.initials: X
authors.lastname: Zhou
authors.affiliation: Key Laboratory of Laboratory Medicine, Ministry of Education of China, School of Laboratory Medicine and Life Science, Wenzhou Medical University, Wenzhou, Zhejiang, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Ye
authors.affiliation: Daicun Town Community Health Service Center, Xiaoshan District, Hangzhou, Zhejiang, China.
authors.forename: Senhai
authors.initials: S
authors.lastname: Yu
authors.affiliation: Xiaoshan District Sixth People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Huabin
authors.initials: H
authors.lastname: Li
authors.affiliation: Xiaoshan District Third People's Hospital, Hangzhou, Zhejiang, China.
authors.forename: Libin
authors.initials: L
authors.lastname: Cai
authors.affiliation: Putuo District People's Hospital, Zhoushan, Zhejiang, China.
authors.forename: Chengguo
authors.initials: C
authors.lastname: Liu
authors.affiliation: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China.
authors.forename: Lixin
authors.initials: L
authors.lastname: Wang
authors.affiliation: The Endocrine Institute and Liaoning Provincial Key Laboratory of Endocrine Diseases, Department of Endocrinology and Metabolism, The First Hospital of China Medical University, Shenyang, Liaoning, China.
authors.forename: Yaxin
authors.initials: Y
authors.lastname: Lai
authors.affiliation: Putuo District People's Hospital, Zhoushan, Zhejiang, China.
authors.forename: Liansheng
authors.initials: L
authors.lastname: Ruan
authors.affiliation: Putuo District People's Hospital, Zhoushan, Zhejiang, China.
authors.forename: Zhanhang
authors.initials: Z
authors.lastname: Sun
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.affiliation: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Yuyang
authors.initials: Y
authors.lastname: Xu
authors.affiliation: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Ling
authors.affiliation: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.|Zhejiang Provincial Center for Disease Control and Prevention, Hangzhou, Zhejiang, China.
authors.forename: Chunxiao
authors.initials: C
authors.lastname: Xu
authors.affiliation: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Yan
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Duo
authors.initials: D
authors.lastname: Lv
authors.affiliation: Department of Epidemiology & Biostatistics, Zhejiang University School of Public Health, Hangzhou, Zhejiang, China.
authors.forename: Zheping
authors.initials: Z
authors.lastname: Yuan
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Jing
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Yingqi
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Bio-X Institutes, Key Laboratory for the Genetics of Developmental and Neuropsychiatric Disorders (Ministry of Education), Shanghai Jiao Tong University, Shanghai, China.|Institute of Social Cognitive and Behavioral Sciences, Shanghai Jiao Tong University, Shanghai, China.
authors.forename: Yongyong
authors.initials: Y
authors.lastname: Shi
authors.affiliation: Department of Pathology, Zhejiang University School of Medicine, Hangzhou, Zhejiang, China.|Key Laboratory of Disease Proteomics of Zhejiang Province, Hangzhou, Zhejiang, China.
authors.forename: Maode
authors.initials: M
authors.lastname: Lai
mesh_terms: D000328:Adult; D000428:Alcohol Drinking / Q000235:genetics / Q000473:pathology; D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000235:genetics*; D000483:Alleles; D000072040:Apolipoprotein A-V / Q000235:genetics*; D002681:China; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D024821:Metabolic Syndrome / Q000235:genetics* / Q000473:pathology; D020641:Polymorphism, Single Nucleotide; D016601:RNA-Binding Proteins / Q000235:genetics*; D014280:Triglycerides / Q000097:blood / Q000235:genetics
chemical_list: D000072040:Apolipoprotein A-V; C000595434:BUD13 homolog protein, human; D016601:RNA-Binding Proteins; D014280:Triglycerides; C096127:ALDH2 protein, human; D000071396:Aldehyde Dehydrogenase, Mitochondrial
keywords: gene-environment interaction; genome-wide association study; metabolic syndrome; secondary signal; single-nucleotide polymorphism