title: Significant Association Between CAV1 Variant rs3807989 on 7p31 and Atrial Fibrillation in a Chinese Han Population.
abstract: BACKGROUND
  Recent genome-wide association studies (GWAS) in European ancestry populations revealed several genomic loci for atrial fibrillation (AF). We previously replicated the 4q25 locus (PITX2) and 16q22 locus (ZFHX3) in the Chinese population, but not the KCNN3 locus on 1q21. With single-nucleotide polymorphism rs3807989 in CAV1 encoding caveolin-1, however, controversial results were reported in 2 Chinese replication studies.
  
  
  RESULTS
  Six remaining AF genetic loci from GWAS, including rs3807989/CAV1, rs593479/PRRX1, rs6479562/C9orf3, rs10824026/SYNPO2L, rs1152591/SYNE2, and rs7164883/HCN4, were analyzed in a Chinese Han population with 941 cases and 562 controls. Only rs3807989 showed significant association with AF (Padj=4.77×10(-5)), and the finding was replicated in 2 other independent populations with 709 cases and 2175 controls, 463 cases and 644 controls, and the combined population with a total of 2113 cases and 3381 controls (Padj=2.20×10(-9); odds ratio [OR]=1.34 for major allele G). Meta-analysis, together with data from previous reports in Chinese and Japanese populations, also showed a significant association between rs3807989 and AF (P=3.40×10(-4); OR=1.24 for allele G). We also found that rs3807989 showed a significant association with lone AF in 3 independent populations and in the combined population (Padj=3.85×10(-8); OR=1.43 for major allele G).
  
  
  CONCLUSIONS
  The data in this study revealed a significant association between rs3807989 and AF in the Chinese Han population. Together with the findings that caveolin-1 interacts with potassium channels Kir2.1, KCNH2, and HCN4 and sodium channels Nav1.5 and Nav1.8, CAV1 becomes a strong candidate susceptibility gene for AF across different ethnic populations. This study is the first to show a significant association between rs3807989 and lone AF.
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (S.C., C.W., X.W., C.X., M.W., P.W., X.T., Q.K.W.).
authors.forename: Shanshan
authors.initials: S
authors.lastname: Chen
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (S.C., C.W., X.W., C.X., M.W., P.W., X.T., Q.K.W.).
authors.forename: Chuchu
authors.initials: C
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (S.C., C.W., X.W., C.X., M.W., P.W., X.T., Q.K.W.).
authors.forename: Xiaojing
authors.initials: X
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (S.C., C.W., X.W., C.X., M.W., P.W., X.T., Q.K.W.).
authors.forename: Chengqi
authors.initials: C
authors.lastname: Xu
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (S.C., C.W., X.W., C.X., M.W., P.W., X.T., Q.K.W.).
authors.forename: Manman
authors.initials: M
authors.lastname: Wu
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (S.C., C.W., X.W., C.X., M.W., P.W., X.T., Q.K.W.).
authors.forename: Pengxia
authors.initials: P
authors.lastname: Wang
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (S.C., C.W., X.W., C.X., M.W., P.W., X.T., Q.K.W.).
authors.forename: Xin
authors.initials: X
authors.lastname: Tu
authors.affiliation: Key Laboratory of Molecular Biophysics of the Ministry of Education, Cardio-X Institute, College of Life Science and Technology and Center for Human Genome Research, Huazhong University of Science and Technology, Wuhan, China (S.C., C.W., X.W., C.X., M.W., P.W., X.T., Q.K.W.) Center for Cardiovascular Genetics, Department of Molecular Cardiology, Lerner Research Institute, Cleveland Clinic, Cleveland, OH (Q.K.W.) Department of Molecular Medicine, Department of Genetics and Genome Sciences, CCLCM, Case Western Reserve University, Cleveland, OH (Q.K.W.).
authors.forename: Qing K
authors.initials: QK
authors.lastname: Wang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001281:Atrial Fibrillation / Q000235:genetics*; D051242:Caveolin 1 / Q000235:genetics*; D002681:China; D005260:Female; D056726:Genetic Association Studies / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors
chemical_list: C495540:CAV1 protein, human; D051242:Caveolin 1
keywords: CAV1; atrial fibrillation; genome‐wide association studies (GWAS); rs3807989; single‐nucleotide polymorphism