Abstract
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.
Highlights
Congenital heart disease (CHD) usually refers to abnormalities in the heart’s structure or function that arise before birth [1]
Our findings suggest that susceptibility loci of atrial septal defect (ASD) identified from Cordell’s European genome-wide association study (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
We attempted to replicate the 4p16 ASD susceptibility loci in Han Chinese population and found that our results were consistent with the results presented by Cordell et al to a certain extent
Summary
Congenital heart disease (CHD) usually refers to abnormalities in the heart’s structure or function that arise before birth [1]. As the most frequent birth defect, CHD affects about 0.8% of live births [2,3], and it is a leading cause of perinatal and infant mortality, causing more than 220,000 deaths globally every year [4]. In China, epidemiological studies suggest an obvious increasing trend of CHD mortality with the overall mortality rate increasing from 141 in 2003 to 229 in 2010 per 10,000,000 person-years [5]. CHD can be classified into three broad categories: cyanotic heart disease, left-sided obstruction defects and septation defects [1]. Several genes linked to CHD have been identified, including T-box transcription factors (TBX1, TBX5 and TBX20), homobox transcription factors (NKX2.5 and NKX2.6), basic helix-loop-helix transcription factors (HAND1 and HAND2), and GATA binding protein 4 (GATA4) [9]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
