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

Terri L Beaty, Ingo Ruczinski, Jeffrey C. Murray, Mary L. Marazita, Ronald G. Munger, Jacqueline B. Hetmanski, Tanda Murray, Richard Redett, Daniele Daniele Fallin, Kung Yee Liang, Tao Wu, Poorav J. Patel, Sheng Chih Jin, Tian Xiao Zhang, Holger Schwender, Yah Huei Wu-Chou, Philip K. Chen, Samuel S. Chong, Felicia Cheah, Vincent YeowXiaoqian Ye, Hong Wang, Shangzhi Huang, Ethylin W. Jabs, Bing Shi, Allen J. Wilcox, Rolv T. Lie, Sun Ha Jee, Kaare Christensen, Kimberly Doheny, Elizabeth Pugh, Hua Ling, Alan F Scott

Research output: Contribution to journalArticle

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.

Original languageEnglish (US)
Pages (from-to)469-478
Number of pages10
JournalGenetic Epidemiology
Volume35
Issue number6
DOIs
StatePublished - Sep 2011

Fingerprint

Gene-Environment Interaction
Cleft Palate
Single Nucleotide Polymorphism
Genome
Mothers
Logistic Models
Smoking
Genes
Maternal Exposure
Chromosomes, Human, Pair 9
Genome-Wide Association Study
First Pregnancy Trimester
Alcohol Drinking
Alcohols

Keywords

  • Cleft palate
  • Gene-environment interaction
  • Genome wide association studies

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate. / Beaty, Terri L; Ruczinski, Ingo; Murray, Jeffrey C.; Marazita, Mary L.; Munger, Ronald G.; Hetmanski, Jacqueline B.; Murray, Tanda; Redett, Richard; Fallin, Daniele Daniele; Liang, Kung Yee; Wu, Tao; Patel, Poorav J.; Jin, Sheng Chih; Zhang, Tian Xiao; Schwender, Holger; Wu-Chou, Yah Huei; Chen, Philip K.; Chong, Samuel S.; Cheah, Felicia; Yeow, Vincent; Ye, Xiaoqian; Wang, Hong; Huang, Shangzhi; Jabs, Ethylin W.; Shi, Bing; Wilcox, Allen J.; Lie, Rolv T.; Jee, Sun Ha; Christensen, Kaare; Doheny, Kimberly; Pugh, Elizabeth; Ling, Hua; Scott, Alan F.

In: Genetic Epidemiology, Vol. 35, No. 6, 09.2011, p. 469-478.

Research output: Contribution to journalArticle

Beaty, TL, Ruczinski, I, Murray, JC, Marazita, ML, Munger, RG, Hetmanski, JB, Murray, T, Redett, R, Fallin, DD, Liang, KY, Wu, T, Patel, PJ, Jin, SC, Zhang, TX, Schwender, H, Wu-Chou, YH, Chen, PK, Chong, SS, Cheah, F, Yeow, V, Ye, X, Wang, H, Huang, S, Jabs, EW, Shi, B, Wilcox, AJ, Lie, RT, Jee, SH, Christensen, K, Doheny, K, Pugh, E, Ling, H & Scott, AF 2011, 'Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate', Genetic Epidemiology, vol. 35, no. 6, pp. 469-478. https://doi.org/10.1002/gepi.20595
Beaty, Terri L ; Ruczinski, Ingo ; Murray, Jeffrey C. ; Marazita, Mary L. ; Munger, Ronald G. ; Hetmanski, Jacqueline B. ; Murray, Tanda ; Redett, Richard ; Fallin, Daniele Daniele ; Liang, Kung Yee ; Wu, Tao ; Patel, Poorav J. ; Jin, Sheng Chih ; Zhang, Tian Xiao ; Schwender, Holger ; Wu-Chou, Yah Huei ; Chen, Philip K. ; Chong, Samuel S. ; Cheah, Felicia ; Yeow, Vincent ; Ye, Xiaoqian ; Wang, Hong ; Huang, Shangzhi ; Jabs, Ethylin W. ; Shi, Bing ; Wilcox, Allen J. ; Lie, Rolv T. ; Jee, Sun Ha ; Christensen, Kaare ; Doheny, Kimberly ; Pugh, Elizabeth ; Ling, Hua ; Scott, Alan F. / Evidence for gene-environment interaction in a genome wide study of nonsyndromic cleft palate. In: Genetic Epidemiology. 2011 ; Vol. 35, No. 6. pp. 469-478.
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AU - Marazita, Mary L.

AU - Munger, Ronald G.

AU - Hetmanski, Jacqueline B.

AU - Murray, Tanda

AU - Redett, Richard

AU - Fallin, Daniele Daniele

AU - Liang, Kung Yee

AU - Wu, Tao

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AU - Jin, Sheng Chih

AU - Zhang, Tian Xiao

AU - Schwender, Holger

AU - Wu-Chou, Yah Huei

AU - Chen, Philip K.

AU - Chong, Samuel S.

AU - Cheah, Felicia

AU - Yeow, Vincent

AU - Ye, Xiaoqian

AU - Wang, Hong

AU - Huang, Shangzhi

AU - Jabs, Ethylin W.

AU - Shi, Bing

AU - Wilcox, Allen J.

AU - Lie, Rolv T.

AU - Jee, Sun Ha

AU - Christensen, Kaare

AU - Doheny, Kimberly

AU - Pugh, Elizabeth

AU - Ling, Hua

AU - Scott, Alan F

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