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Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate.

 Terri H. Beaty  ;  Ingo Ruczinski  ;  Jeffrey C. Murray  ;  Mary L. Marazita  ;  Ronald G. Munger  ;  Jacqueline B. Hetmanski  ;  Tanda Murray  ;  Richard J. Redett  ;  M. Daniele Fallin  ;  Kung Yee Liang  ;  Tao Wu  ;  Poorav J. Patel  ;  Sheng C. Jin  ;  Tian Xiao Zhang  ;  Holger Schwender  ;  Yah Huei Wu-Chou  ;  Philip K Chen  ;  Samuel S Chong  ;  Felicia Cheah  ;  Vincent Yeow  ;  Xiaoqian Ye  ;  Hong Wang  ;  Shangzhi Huang  ;  Ethylin W. Jabs  ;  Bing Shi1  ;  Allen J. Wilcox  ;  Rolv T. Lie1  ;  Sun Ha Jee  ;  Kaare Christensen  ;  Kimberley F. Doheny  ;  Elizabeth W. Pugh  ;  Hua Ling  ;  Alan F. Scott 
 GENETIC EPIDEMIOLOGY, Vol.35(6) : 469-478, 2011 
Journal Title
Issue Date
Alcohol Drinking ; Chromosome Mapping ; Cleft Palate/chemically induced ; Cleft Palate/etiology ; Cleft Palate/genetics* ; Female ; Gene-Environment Interaction ; Genome-Wide Association Study ; Genotype ; Humans ; Male ; Maternal Exposure ; Models, Genetic ; Parents ; Polymorphism, Single Nucleotide ; Pregnancy ; Risk ; Vitamins/therapeutic use
gene-environment interaction ; cleft palate ; genome wide association studies
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.
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4. Graduate School of Public Health (보건대학원) > Graduate School of Public Health (보건대학원) > 1. Journal Papers
Yonsei Authors
Jee, Sun Ha(지선하) ORCID logo https://orcid.org/0000-0001-9519-3068
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