2 research outputs found
A Genome-Wide association Study of Obstructive Heart Defects among Participants in the National Birth Defects Prevention Study
Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (
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A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study.
Obstructive heart defects (OHDs) share common structural lesions in arteries and cardiac valves, accounting for ~25% of all congenital heart defects. OHDs are highly heritable, resulting from interplay among maternal exposures, genetic susceptibilities, and epigenetic phenomena. A genome-wide association study was conducted in National Birth Defects Prevention Study participants (Ndiscovery = 3978; Nreplication = 2507), investigating the genetic architecture of OHDs using transmission/disequilibrium tests (TDT) in complete case-parental trios (Ndiscovery_TDT = 440; Nreplication_TDT = 275) and case-control analyses separately in infants (Ndiscovery_CCI = 1635; Nreplication_CCI = 990) and mothers (case status defined by infant; Ndiscovery_CCM = 1703; Nreplication_CCM = 1078). In the TDT analysis, the SLC44A2 single nucleotide polymorphism (SNP) rs2360743 was significantly associated with OHD (pdiscovery = 4.08βΓβ10-9 ; preplication = 2.44βΓβ10-4 ). A CAPN11 SNP (rs55877192) was suggestively associated with OHD (pdiscovery = 1.61βΓβ10-7 ; preplication = 0.0016). Two other SNPs were suggestively associated (pβ<β1βΓβ10-6 ) with OHD in only the discovery sample. In the case-control analyses, no SNPs were genome-wide significant, and, even with relaxed thresholds (βΓβdiscovery β<β1βΓβ10-5 and preplication β<β0.05), only one SNP (rs188255766) in the infant analysis was associated with OHDs (pdiscovery = 1.42βΓβ10-6 ; preplication = 0.04). Additional SNPs with pdiscovery β<β1βΓβ10-5 were in loci supporting previous findings but did not replicate. Overall, there was modest evidence of an association between rs2360743 and rs55877192 and OHD and some evidence validating previously published findings