Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

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

doi:10.1371/journal.pone.0088088

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Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

Journal article

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Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate

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, …

PloS one, Vol.9(2), pp.e88088-e88088

2014

DOI: 10.1371/journal.pone.0088088

PMCID: PMC3916361

PMID: 24516586

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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.

Genetic Predisposition to Disease

Humans

Risk Factors

Asian Continental Ancestry Group - genetics

Logistic Models

Male

Cleft Palate - genetics

Chromosomes, Human, Pair 4 - genetics

Gene-Environment Interaction

Tobacco Smoke Pollution - adverse effects

Polymorphism, Single Nucleotide - genetics

Female

Glucose Transport Proteins, Facilitative - genetics

Microfilament Proteins - genetics

Details

Title: Subtitle: Evidence of gene-environment interaction for two genes on chromosome 4 and environmental tobacco smoke in controlling the risk of nonsyndromic cleft palate
Creators: Tao Wu - Peking University Health Science Center, Beijing, China ; Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America
Holger Schwender - Mathematical Institute, Heinrich Heine University Duesseldorf, Duesseldorf, Germany
Ingo Ruczinski - Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America
Jeffrey C Murray - University of Iowa, Children's Hospital, Iowa City, Iowa, United States of America
Mary L Marazita - Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania, United States of America
Ronald G Munger - Utah State University, Logan, Utah, United States of America
Jacqueline B Hetmanski - Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America
Margaret M Parker - Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America
Ping Wang - Peking University Health Science Center, Beijing, China
Tanda Murray - Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America
Margaret Taub - Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America
Shuai Li - Peking University Health Science Center, Beijing, China
Richard J Redett - Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America
M Daniele Fallin - Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America
Kung Yee Liang - Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America ; National Yang-Ming University, Taipei, Taiwan
Yah Huei Wu-Chou - Chang Gung Memorial Hospital, Taoyuan, Taiwan
Samuel S Chong - National University of Singapore, Singapore, Singapore
Vincent Yeow - KK Women's & Children's Hospital, Singapore, Singapore
Xiaoqian Ye - Wuhan University, School of Stomatology, Wuhan, China ; Mount Sinai Medical Center, New York, New York, United States of America
Hong Wang - Peking University Health Science Center, Beijing, China
Shangzhi Huang - Peking Union Medical College, Beijing, China
Ethylin W Jabs - Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America ; Mount Sinai Medical Center, New York, New York, United States of America
Bing Shi - State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu, China
Allen J Wilcox - NIEHS/NIH, Epidemiology Branch, Durham, North Carolina, United States of America
Sun Ha Jee - Yonsei University, School of Public Health, Seoul, Korea
Alan F Scott - Johns Hopkins University, School of Medicine, Baltimore, Maryland, United States of America
Terri H Beaty - Johns Hopkins University, School of Public Health, Baltimore, Maryland, United States of America
Resource Type: Journal article
Publication Details: PloS one, Vol.9(2), pp.e88088-e88088
DOI: 10.1371/journal.pone.0088088
PMID: 24516586
PMCID: PMC3916361
NLM abbreviation: PLoS One
ISSN: 1932-6203
eISSN: 1932-6203
Publisher: Public Library of Science; United States
Grant note: D43 TW06176 / FIC NIH HHS U01 DE020073 / NIDCR NIH HHS P50 DE016215 / NIDCR NIH HHS R01 DE016148 / NIDCR NIH HHS R21 DE016930 / NIDCR NIH HHS U01 HG004446 / NHGRI NIH HHS U01-DE-018993 / NIDCR NIH HHS R01-DE-014581 / NIDCR NIH HHS P50-DE-016215 / NIDCR NIH HHS U01 DE018993 / NIDCR NIH HHS R01-DE-012472 / NIDCR NIH HHS R01-DE-016148 / NIDCR NIH HHS U01- HG004446 / NHGRI NIH HHS R37-DE-0-8559 / NIDCR NIH HHS R01 DE014581 / NIDCR NIH HHS R01-DE-0106877 / NIDCR NIH HHS D43 TW006176 / FIC NIH HHS R37-DE-08559 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS U01-DE-020057 / NIDCR NIH HHS U01 DE020057 / NIDCR NIH HHS R01 DE009886 / NIDCR NIH HHS R21-DE-016930 / NIDCR NIH HHS R01-DE-09886 / NIDCR NIH HHS
Language: English
Date published: 2014
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
Record Identifier: 9984025451102771

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