Replication of the 4p16 Susceptibility Locus in Congenital Heart Disease in Han Chinese PopulationsReport as inadecuate




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Congenital heart disease CHD is the most common form of congenital human birth anomalies and a leading cause of perinatal and infant mortality. Some studies including our published genome-wide association study GWAS of CHD have indicated that genetic variants may contribute to the risk of CHD. Recently, Cordell et al. published a GWAS of multiple CHD phenotypes in European Caucasians and identified 3 susceptibility loci rs870142, rs16835979 and rs6824295 for ostium secundum atrial septal defect ASD at chromosome 4p16. However, whether these loci at 4p16 confer the predisposition to CHD in Chinese population is unclear. In the current study, we first analyzed the associations between these 3 single nucleotide polymorphisms SNPs at 4p16 and CHD risk by using our existing genome-wide scan data and found all of the 3 SNPs showed significant associations with ASD in the same direction as that observed in Cordell’s study, but not with other subtypes- ventricular septal defect VSD and ASD combined VSD. As these 3 SNPs were in high linkage disequilibrium LD in Chinese population, we selected one SNP with the lowest P value in our GWAS scan rs16835979 to perform a replication study with additional 1,709 CHD cases with multiple phenotypes and 1,962 controls. The significant association was also observed only within the ASD subgroup, which was heterogeneous from other disease groups. In combined GWAS and replication samples, the minor allele of rs16835979 remained significant association with the risk of ASD OR = 1.22, 95% CI = 1.08–1.38, P = 0.001. Our findings suggest that susceptibility loci of ASD identified from Cordell’s European GWAS are generalizable to Chinese population, and such investigation may provide new insights into the roles of genetic variants in the etiology of different CHD phenotypes.



Author: Bijun Zhao , Yuan Lin , Jing Xu, Bixian Ni, Min Da, Chenyue Ding, Yuanli Hu, Kai Zhang, Shiwei Yang, Xiaowei Wang, Shiqiang Yu, Y

Source: http://plos.srce.hr/



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