Journal article
Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate
Genetic epidemiology, Vol.35(6), pp.469-478
09/2011
DOI: 10.1002/gepi.20595
PMCID: PMC3180858
PMID: 21618603
Abstract
Nonsyndromic cleft palate (CP) is a common birth defect with a complex and heterogeneous etiology involving both genetic and environmental risk factors. We conducted a genome-wide association study (GWAS) using 550 case-parent trios, ascertained through a CP case collected in an international consortium. Family-based association tests of single nucleotide polymorphisms (SNP) and three common maternal exposures (maternal smoking, alcohol consumption, and multivitamin supplementation) were used in a combined 2 df test for gene (G) and gene-environment (G × E) interaction simultaneously, plus a separate 1 df test for G × E interaction alone. Conditional logistic regression models were used to estimate effects on risk to exposed and unexposed children. While no SNP achieved genome-wide significance when considered alone, markers in several genes attained or approached genome-wide significance when G × E interaction was included. Among these, MLLT3 and SMC2 on chromosome 9 showed multiple SNPs resulting in an increased risk if the mother consumed alcohol during the peri-conceptual period (3 months prior to conception through the first trimester). TBK1 on chr. 12 and ZNF236 on chr. 18 showed multiple SNPs associated with higher risk of CP in the presence of maternal smoking. Additional evidence of reduced risk due to G × E interaction in the presence of multivitamin supplementation was observed for SNPs in BAALC on chr. 8. These results emphasize the need to consider G × E interaction when searching for genes influencing risk to complex and heterogeneous disorders, such as nonsyndromic CP.
Details
- Title: Subtitle
- Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate
- Creators
- Terri H Beaty - School of Public Health, Johns Hopkins University, 615 N. Wolfe St., Baltimore, Maryland, USA. tbeaty@jhsph.eduIngo RuczinskiJeffrey C MurrayMary L MarazitaRonald G MungerJacqueline B HetmanskiTanda MurrayRichard J RedettM Daniele FallinKung Yee LiangTao WuPoorav J PatelSheng-Chih JinTian Xiao ZhangHolger SchwenderYah Huei Wu-ChouPhilip K ChenSamuel S ChongFelicia CheahVincent YeowXiaoqian YeHong WangShangzhi HuangEthylin W JabsBing ShiAllen J WilcoxRolv T LieSun Ha JeeKaare ChristensenKimberley F DohenyElizabeth W PughHua LingAlan F Scott
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.35(6), pp.469-478
- DOI
- 10.1002/gepi.20595
- PMID
- 21618603
- PMCID
- PMC3180858
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Publisher
- United States
- Grant note
- P50 DE016215 / NIDCR NIH HHS R01 DE016148 / NIDCR NIH HHS R21 DE016930 / NIDCR NIH HHS U01 DE018993-01 / NIDCR NIH HHS U01 HG004446 / NHGRI NIH HHS U01-DE-018993 / NIDCR NIH HHS R01-DE-014581 / NIDCR NIH HHS P50-DE-016215 / NIDCR NIH HHS U01 DE018993 / NIDCR NIH HHS R01-DE-012472 / NIDCR NIH HHS R01 DE014581-01A2 / NIDCR NIH HHS R01-DE-016148 / NIDCR NIH HHS Intramural NIH HHS R37-DE-0-8559 / NIDCR NIH HHS R01 DE014581 / NIDCR NIH HHS R01-DE-0106877 / NIDCR NIH HHS R37-DE-08559 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS U01-DE-020057 / NIDCR NIH HHS U01 DE020057 / NIDCR NIH HHS R01 DE009886 / NIDCR NIH HHS R21-DE-016930 / NIDCR NIH HHS R01-DE-09886 / NIDCR NIH HHS
- Language
- English
- Date published
- 09/2011
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Orthopedics and Rehabilitation; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
- Record Identifier
- 9984025355502771
Metrics
19 Record Views