title: Association between the European GWAS-identified susceptibility locus at chromosome 4p16 and the risk of atrial septal defect: a case-control study in Southwest China and a meta-analysis.
abstract: Atrial septal defect (ASD) is the third most frequent type of congenital heart anomaly, featuring shunting of blood between the two atria. Gene-environment interaction remains to be an acknowledged cause for ASD occurrence. A recent European genome-wide association study (GWAS) of congenital heart disease (CHD) identified 3 susceptibility SNPs at chromosome 4p16 associated with ASD: rs870142, rs16835979 and rs6824295. A Chinese-GWAS of CHD conducted in the corresponding period did not reveal the 3 susceptibility SNPs, but reported 2 different risk SNPs: rs2474937 and rs1531070. Therefore, we aimed to investigate the associations between the 3 European GWAS-identified susceptibility SNPs and ASD risk in the Han population in southwest China. Additionally, to increase the robustness of our current analysis, we conducted a meta-analysis combining published studies and our current case-control study. We performed association, linkage disequilibrium, and haplotype analysis among the 3 SNPs in 190 ASD cases and 225 age-, sex-, and ethnicity-matched healthy controls. Genotype and allele frequencies among the 3 SNPs showed statistically significant differences between the cases and controls. Our study found that individuals carrying the allele T of rs870142, the allele A of rs16835979, and the allele T of rs6824295 had a respective 50.1% (odds ratio (OR) = 1.501, 95% confidence interval (CI) = 1.122-2.009, PFDR-BH = 0.018), 48.5% (OR = 1.485, 95%CI = 1.109-1.987, PFDR-BH = 0.012), and 38.6% (OR = 1.386, 95%CI = 1.042-1.844, PFDR-BH = 0.025) increased risk to develop ASD than wild-type allele carriers in our study cohort. In the haplotype analysis, we identified a disease-risk haplotype (TAT) (OR = 1.540, 95%CI = 1.030-2.380, PFDR-BH = 0.016). Our meta-analysis also showed that the investigated SNP was associated with ASD risk (combined OR (95%CI) = 1.35 (1.24-1.46), P < 0.00001). Our study provides compelling evidence to motivate better understanding of the etiology of ASD.
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Li
authors: L
authors: Zhao
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Bei
authors: B
authors: Li
authors: Department of Cardiothoracic Surgery, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Ke
authors: K
authors: Dian
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Binwu
authors: B
authors: Ying
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Xiaojun
authors: X
authors: Lu
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Xuejiao
authors: X
authors: Hu
authors: Department of Cardiothoracic Surgery, West China Hospital, Sichuan University, Chengdu, P.R. China.
authors: Qi
authors: Q
authors: An
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Chunxia
authors: C
authors: Chen
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Chunyan
authors: C
authors: Huang
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Bin
authors: B
authors: Tan
authors: Department of Laboratory Medicine, West China Hospital, Sichuan University, Chengdu, P. R. China.
authors: Li
authors: L
authors: Qin
mesh_terms: D016022:Case-Control Studies; D002681:China; D002894:Chromosomes, Human, Pair 4 / Q000235:genetics*; D005060:Europe; D005260:Female; D056426:Genetic Loci; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D006239:Haplotypes / Q000235:genetics; D006344:Heart Septal Defects, Atrial / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D012307:Risk Factors; D055815:Young Adult