@article{841629adb9234aa29ba5df8ddb300ab8,
title = "Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate",
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.",
author = "Tao Wu and Holger Schwender and Ingo Ruczinski and Murray, {Jeffrey C.} and Marazita, {Mary L.} and Munger, {Ronald G.} and Hetmanski, {Jacqueline B.} and Parker, {Margaret M.} and Ping Wang and Tanda Murray and Margaret Taub and Shuai Li and Redett, {Richard J.} and Fallin, {M. Daniele} and Liang, {Kung Yee} and Wu-Chou, {Yah Huei} and Chong, {Samuel S.} and Vincent Yeow and Xiaoqian Ye and Hong Wang and Shangzhi Huang and Jabs, {Ethylin W.} and Bing Shi and Wilcox, {Allen J.} and Jee, {Sun Ha} and Scott, {Alan F.} and Beaty, {Terri H.}",
note = "Funding Information: We sincerely thank all of the families at each recruitment site for participating in this study, and we gratefully acknowledge the invaluable assistance of clinical, field and laboratory staff who contributed to making this work possible. Funding to support data collection, genotyping and analysis came from several sources, some to individual investigators (R01-DE-014581, R01-DE-016148, P50-DE-016215, R21-DE-016930, R01-DE-09886, R37-DE-08559, U01-DE-020057, R37-DE-0-8559, U01-DE-020057, R01-DE-012472, R01-DE-0106877) and some to the cleft consortium itself (U01-DE-018993). This project was part of the Gene, Environment Association Studies (GENEVA) Consortium funded by the National Human Genome Research Institute (NHGRI) to enhance communication and collaboration among researchers conducting genome-wide studies of complex diseases. Our group benefited greatly from the efforts of the entire consortium, especially the Coordinating Center (directed by B. Weir and C. Laurie of the University of Washington; U01- HG004446) in data cleaning and preparation for submission to the Database for Genotypes and Phenotypes (dbGaP). We also acknowledge the leadership of T. Manolio of NHGRI and E. Harris of National Institute of Dental and Craniofacial Research (NIDCR). Genotyping services were provided by the Center for Inherited Disease Research (CIDR). The International Cleft Consortium including genotyping and analysis was supported by the National Institute for Dental and Craniofacial Research through U01-DE-018993; “International Consortium to Identify Genes & Interactions Controlling Oral Clefts”, 2007–2009; TH Beaty, PI. T Wu was supported by the International Collaborative Genetics Research Training Program (ICGRTP, NIH D43 TW06176) and “The genome wide association study of nonsyndromic oral clefts in Chinese populations using case parent trios design” (81102178, 2012–2014) from National Natural Science Foundation of China.",
year = "2014",
month = feb,
day = "6",
doi = "10.1371/journal.pone.0088088",
language = "English (US)",
volume = "9",
journal = "PLoS One",
issn = "1932-6203",
publisher = "Public Library of Science",
number = "2",
}