Evidence of Gene−Environment Interaction for Two Genes on Chromosome 4 and Environmental Tobacco Smoke in Controlling the Risk of Nonsyndromic Cleft Palate
Year: 2014
Type: article
Study design: Observational Study
Abstract: Nonsyndromic cleft palate (CP) is one of the most common human birth defects and both genetic and environmental risk factors contribute to its etiology. We conducted a genome-wide association study (GWAS) using 550 CP case-parent trios ascertained in an international consortium. Stratified analysis among trios with different ancestries was performed to test for GxE interactions with common maternal exposures using conditional logistic regression models. While no single nucleotide polymorphism (SNP) achieved genome-wide significance when considered alone, markers in SLC2A9 and the neighboring WDR1 on chromosome 4p16.1 gave suggestive evidence of gene-environment interaction with environmental tobacco smoke (ETS) among 259 Asian trios when the models included a term for GxE interaction. Multiple SNPs in these two genes were associated with increased risk of nonsyndromic CP if the mother was exposed to ETS during the peri-conceptual period (3 months prior to conception through the first trimester). When maternal ETS was considered, fifteen of 135 SNPs mapping to SLC2A9 and 9 of 59 SNPs in WDR1 gave P values approaching genome-wide significance (10(-6)<P<10(-4)) in a test for GxETS interaction. SNPs rs3733585 and rs12508991 in SLC2A9 yielded P = 2.26×10(-7) in a test for GxETS interaction. SNPs rs6820756 and rs7699512 in WDR1 also yielded P = 1.79×10(-7) and P = 1.98×10(-7) in a 1 df test for GxE interaction. Although further replication studies are critical to confirming these findings, these results illustrate how genetic associations for nonsyndromic CP can be missed if potential GxE interaction is not taken into account, and this study suggest SLC2A9 and WDR1 should be considered as candidate genes for CP.
Source: PLoS ONE
Authors: Tao Wu, Holger Schwender, Ingo Ruczinski, Jeffrey C. Murray, Mary L. Marazita, Ronald G. Munger, Jacqueline B. Hetmanski, Margaret M. Parker, Ping Wang, Tanda Murray, Margaret Taub, Shuai Li, Richard J. Redett, M. Daniele Fallin, Kung Yee Liang, Yah Huei Wu-Chou, Samuel S. Chong, Vincent Yeow, Xiaoqian Ye, Hong Wang, Shangzhi Huang, Ethylin W. Jabs, Bing Shi, Allen J. Wilcox, Sun Ha Jee, Alan F. Scott, Terri H. Beaty
Institutions: Johns Hopkins University, Peking University, Heinrich Heine University Düsseldorf, University of Iowa Stead Family Children’s Hospital, University of Pittsburgh, Utah State University, National Yang Ming University, Chang Gung Memorial Hospital, Taoyuan Chang Gung Memorial Hospital, Linkou Chang Gung Memorial Hospital, National University of Singapore, KK Women's and Children's Hospital, Mount Sinai Hospital, Wuhan University, Chinese Academy of Medical Sciences & Peking Union Medical College, Sichuan University, State Key Laboratory of Oral Diseases, National Institutes of Health, National Institute of Environmental Health Sciences, Yonsei University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $2,382
Awards: G1015439273, G1305686651, G1417098574, G2026143151, GENE MAPPING STUDIES OF ORAL/FACIAL CLEFTS--CHINA/INDIA, G2407687362, G2823826068, International Consortium to Identify Genes and Interactions Controlling Oral Clef, Extending the Phenotype of Nonsyndromic Orofacial Clefting, Collaborative Genetics Research Training Program, G397206275, G4135332630, G4261463791, Genome Wide Association Coordinating Center, Oral Clefts: Moving from Genome Wide Studies Toward Functional Genomics, G513086327, G6391657209, G6416516086, FaceBase Management and Coordination Hub, International Genetic Epidemiology of Oral Clefts, G8161118679, Planning International Orofacial Cleft Genetic Studies, G9000076949, G9000160421
OpenAlex ID: W2133200119