Evidence for Gene-Environment Interaction in a Genome Wide Study of Nonsyndromic Cleft Palate
In: SCI, 2011
Online
academicJournal
Zugriff:
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 x E) interaction simultaneously, plus a separate 1 df test for G x 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 x 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 x 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 x E interaction when searching for genes influencing risk to complex and heterogeneous disorders, such as nonsyndromic CP. Genet. Epidemiol. 35: 469-478, 2011. (C) 2011 Wiley-Liss, Inc. ; http://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcApp=PARTNER_APP&SrcAuth=LinksAMR&KeyUT=WOS:000294177900005&DestLinkType=FullRecord&DestApp=ALL_WOS&UsrCustomerID=8e1609b174ce4e31116a60747a720701 ; Genetics & Heredity ; Public, Environmental & Occupational Health ; SCI(E) ; 50 ; ARTICLE ; 6 ; 469-478 ; 35
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Evidence for Gene-Environment Interaction in a Genome Wide Study of Nonsyndromic Cleft Palate
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Autor/in / Beteiligte Person: | Beaty, Terri H. ; Ruczinski, Ingo ; Murray, Jeffrey C. ; Marazita, Mary L. ; Munger, Ronald G. ; Hetmanski, Jacqueline B. ; Murray, Tanda ; Redett, Richard J. ; Fallin, M. 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, Kimberley F. ; Pugh, Elizabeth W. ; Ling, Hu ; Beaty, TH (reprint author), Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. ; Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, Baltimore, MD 21205 USA. ; Univ Iowa, Childrens Hosp, Iowa City, IA USA. ; Univ Pittsburgh, Sch Dent Med, Ctr Craniofacial & Dent Genet, Pittsburgh, PA USA. ; Utah State Univ, Logan, UT 84322 USA. ; Natl Yang Ming Univ, Taipei 112, Taiwan. ; Chang Gung Mem Hosp, Tao Yuan, Taiwan. ; Natl Univ Singapore, Singapore 117548, Singapore. ; KK Womens & Childrens Hosp, Singapore, Singapore. ; Peking Univ, Hlth Sci Ctr, Beijing 100871, Peoples R China. ; Wuhan Univ, Sch Stomatol, Wuhan 430072, Peoples R China. ; Peking Union Med Coll, Beijing 100021, Peoples R China. ; Mt Sinai Sch Med, New York, NY USA. ; Sichuan Univ, W China Coll Stomatol, State Key Lab Oral Dis, Chengdu 610064, Peoples R China. ; NIEHS NIH, Epidemiol Branch, Durham, NC USA. ; Univ Bergen, Bergen, Norway. ; Yonsei Univ, Seoul 120749, South Korea. ; Univ So Denmark, Odense, Denmark. ; Johns Hopkins Univ, Sch Med, Ctr Inherited Dis Res, Baltimore, MD 21205 USA. ; Johns Hopkins Univ, Sch Publ Hlth, Dept Epidemiol, 615 N Wolfe St, Baltimore, MD 21205 USA. |
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Zeitschrift: | SCI, 2011 |
Veröffentlichung: | 遗传流行病学, 2011 |
Medientyp: | academicJournal |
ISSN: | 0741-0395 (print) |
DOI: | 10.1002/gepi.20595 |
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