Journal article
A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study
American journal of medical genetics. Part A, Vol.188(8), pp.2303-2314
08/2022
DOI: 10.1002/ajmg.a.62759
PMCID: PMC9283270
PMID: 35451555
Abstract
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 = 4.08 × 10−9; preplication = 2.44 × 10−4). A CAPN11 SNP (rs55877192) was suggestively associated with OHD (pdiscovery = 1.61 × 10−7; preplication = 0.0016). Two other SNPs were suggestively associated (p < 1 × 10−6) with OHD in only the discovery sample. In the case–control analyses, no SNPs were genome-wide significant, and, even with relaxed thresholds ( × discovery < 1 × 10−5 and preplication < 0.05), only one SNP (rs188255766) in the infant analysis was associated with OHDs (pdiscovery = 1.42 × 10−6; preplication = 0.04). Additional SNPs with pdiscovery < 1 × 10−5 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.
Details
- Title: Subtitle
- A genome-wide association study of obstructive heart defects among participants in the National Birth Defects Prevention Study
- Creators
- Sara R Rashkin - University of California, San FranciscoMario Cleves - University of South FloridaGary M Shaw - Stanford UniversityWendy N Nembhard - University of Arkansas for Medical SciencesEirini Nestoridi - Massachusetts Department of Public HealthMary M Jenkins - National Center on Birth Defects and Developmental DisabilitiesPaul A Romitti - University of IowaXiang-Yang Lou - University of FloridaMarilyn L Browne - Department of Epidemiology and Biostatistics, School of Public Health, University at Albany, Rensselaer, New York, USALaura E Mitchell - Department of Epidemiology, Human Genetics, and Environmental Sciences, UTHealth School of Public Health, Houston, Texas, USAAndrew F Olshan - Department of Epidemiology, University of North Carolina, Chapel Hill, North Carolina, USAKevin Lomangino - Kaufman Wills Fusting & Company, Baltimore, Maryland, USASudeepa Bhattacharyya - Bioinformatics and Data Science at University of Arkansas, Little Rock, Arkansas, USAJohn S Witte - University of California, San FranciscoCharlotte A Hobbs - Rady Children's Hospital-San DiegoNational Birth Defects Prevention Study
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.188(8), pp.2303-2314
- DOI
- 10.1002/ajmg.a.62759
- PMID
- 35451555
- PMCID
- PMC9283270
- NLM abbreviation
- Am J Med Genet A
- eISSN
- 1552-4833
- Grant note
- NOFO #DD18-001 / NCBDD CDC HHS FOA #DD13-003 / NCBDD CDC HHS R25 CA112355 / NIH HHS CDC HHS PA #02081 / NCBDD CDC HHS FOA #DD09-001 / NCBDD CDC HHS 5U01DD000491-05 / NCBDD CDC HHS PA #96043 / NCBDD CDC HHS 5R01HD039054-12 / National Institute of Child Health and Human Development
- Language
- English
- Electronic publication date
- 04/22/2022
- Date published
- 08/2022
- Academic Unit
- Epidemiology; Biostatistics
- Record Identifier
- 9984244860102771
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