Association analysis identifies new risk loci for congenital heart disease in Chinese populations.
Our previous genome-wide association study (GWAS) identified two susceptibility loci for congenital heart disease (CHD) in Han Chinese. Here we identify additional loci by testing promising associations in an extended 3-stage validation consisting of 6,053 CHD cases and 7,410 controls. We find GW significant (P<5.0 × 10(-8)) evidence of 4 additional CHD susceptibility loci at 4q31.22 (rs1400558, upstream of EDNRA, Pall=1.63 × 10(-9)), 9p24.2 (rs7863990, close to SMARCA2, Pall=3.71 × 10(-14)), 12q24.13 (rs2433752, upstream of TBX3 and TBX5, Pall=1.04 × 10(-10)) and 20q12 (rs490514, in PTPRT, Pall=1.20 × 10(-13)). Moreover, the data from previous European GWAS supports that rs490514 is associated with the risk of CHD (P=3.40 × 10(-3)). These results enhance our understanding of CHD susceptibility.
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Yuan
Y
Lin
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
Xuejiang
0000000204755705
X
Guo
Department of Cardiovascular Surgery, Xijing hospital, The Fourth Military Medical University, Xi'an 710032, China.
Bijun
B
Zhao
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
Juanjuan
J
Liu
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Min
M
Da
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Yang
Y
Wen
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Yuanli
Y
Hu
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Bixian
B
Ni
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Kai
K
Zhang
Department of Cardiology, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Shiwei
S
Yang
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Jing
J
Xu
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Juncheng
J
Dai
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Xiaowei
X
Wang
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Toxicology and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Yankai
Y
Xia
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Hongxia
H
Ma
Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Guangfu
G
Jin
Department of Cardiovascular Surgery, Xijing hospital, The Fourth Military Medical University, Xi'an 710032, China.
Shiqiang
S
Yu
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Center of Clinical Reproductive Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Jiayin
J
Liu
1] Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK [2] Institute of Cardiovascular Sciences, The University of Manchester, Manchester M13 9NT, UK.
Bernard D
0000000195730812
BD
Keavney
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Judith A
JA
Goodship
Institute of Genetic Medicine, Newcastle University, Newcastle upon Tyne NE1 3BZ, UK.
Heather J
HJ
Cordell
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Toxicology and Key Laboratory of Modern Toxicology of Ministry of Education, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Xinru
X
Wang
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Hongbing
H
Shen
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
Jiahao
J
Sha
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Histology and Embryology, Nanjing Medical University, Nanjing 210029, China.
Zuomin
Z
Zhou
Department of Thoracic and Cardiovascular Surgery, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yijiang
Y
Chen
Department of Cardiothoracic Surgery, Nanjing Children's Hospital, Nanjing Medical University, Nanjing 210008, China.
Xuming
X
Mo
Key Laboratory of Freshwater Fish Reproduction and Development, Ministry of Education, Laboratory of Molecular Developmental Biology, School of Life Sciences, Southwest University, Beibei, Chongqing 400715, China.
Lingfei
L
Luo
1] State Key Laboratory of Reproductive Medicine, Nanjing Medical University, Nanjing 210029, China [2] Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing 211166, China.
Zhibin
Z
Hu
D044466:Asian People / Q000235:genetics*; D016022:Case-Control Studies; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006330:Heart Defects, Congenital / Q000208:ethnology* / Q000235:genetics*; D006801:Humans; D020641:Polymorphism, Single Nucleotide; D015203:Reproducibility of Results