Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts

Min Shi; Jeffrey C Murray; Mary L Marazita; Ronald G Munger; Ingo Ruczinski; Jacqueline B Hetmanski; Tao Wu; Tanda Murray; Richard J Redett; Allen J Wilcox; Rolv T Lie; Ethylin Wang Jabs; Yah Huei Wu-Chou; Philip K Chen; Hong Wang; Xiaoqian Ye; Vincent Yeow; Samuel S Chong; Bing Shi; Kaare Christensen; Alan F Scott; Poorav Patel; Felicia Cheah; Terri H Beaty

doi:10.1002/ajmg.a.35257

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Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts

Journal article

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Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts

Min Shi, Jeffrey C Murray, Mary L Marazita, Ronald G Munger, Ingo Ruczinski, Jacqueline B Hetmanski, Tao Wu, Tanda Murray, Richard J Redett, Allen J Wilcox, …

American journal of medical genetics. Part A, Vol.158A(4), pp.784-794

04/2012

DOI: 10.1002/ajmg.a.35257

PMCID: PMC3617127

PMID: 22419666

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https://www.ncbi.nlm.nih.gov/pmc/articles/3617127View

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Abstract

We performed a genome wide association analysis of maternally-mediated genetic effects and parent-of-origin effects on risk of orofacial clefting using over 2,000 case-parent triads collected through an international cleft consortium. We used log-linear regression models to test individual SNPs. For SNPs with a p-value <10 −5 for maternal genotypic effects, we also applied a haplotype-based method, TRIMM, to extract potential information from clusters of correlated SNPs. None of the SNPs were significant at the genome wide level. Our results suggest neither maternal genome nor parent of origin effects play major roles in the etiology of orofacial clefting in our sample. This finding is consistent with previous genetic studies and recent population-based cohort studies in Norway and Denmark, which showed no apparent difference between mother-to-offspring and father-to-offspring recurrence of clefting. We, however, cannot completely rule out maternal genome or parent of origin effects as risk factors because very small effects might not be detectable with our sample size, they may influence risk through interactions with environmental exposures or may act through a more complex network of interacting genes. Thus the most promising SNPs identified by this study may still be worth further investigation.

GWAS

association study

maternal genes

family-based study

parent-of-origin

Details

Title: Subtitle: Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts
Creators: Min Shi - NIEHS/NIH, Durham, Biostatistics Branch North Carolina
Jeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, IA
Mary L Marazita - University of Pittsburgh, School of Dental Medicine, Pittsburgh, PA
Ronald G Munger - Utah State University, Logan, UT
Ingo Ruczinski - Johns Hopkins University, School of Public Health, Baltimore, MD
Jacqueline B Hetmanski - Johns Hopkins University, School of Public Health, Baltimore, MD
Tao Wu - Johns Hopkins University, School of Public Health, Baltimore, MD
Tanda Murray - Johns Hopkins University, School of Public Health, Baltimore, MD
Richard J Redett - Johns Hopkins University, School of Medicine, Baltimore, MD
Allen J Wilcox - NIEHS/NIH, Durham, Epidemiology Branch North Carolina
Rolv T Lie - University of Bergen, Bergen, Norway
Ethylin Wang Jabs - Mt. Sinai Medical School, New York, NY
Yah Huei Wu-Chou - Chang Gung Memorial Hospital, Taoyuan, Taiwan
Philip K Chen - Chang Gung Memorial Hospital, Taoyuan, Taiwan
Hong Wang - Peking University Health Science Center, Beijing, China
Xiaoqian Ye - Mt. Sinai Medical School, New York, NY
Vincent Yeow - KK Women’s & Children’s Hospital, Singapore
Samuel S Chong - National University of Singapore, Singapore
Bing Shi - State Key Laboratory of Oral Disease, West China College of Stomatology, Sichuan University, Chengdu 610041, P.R. China
Kaare Christensen - University of Southern Denmark, Odense, Denmark
Alan F Scott - Johns Hopkins University, School of Medicine, Baltimore, MD
Poorav Patel - Johns Hopkins University, School of Public Health, Baltimore, MD
Felicia Cheah - National University of Singapore, Singapore
Terri H Beaty - Johns Hopkins University, School of Public Health, Baltimore, MD
Resource Type: Journal article
Publication Details: American journal of medical genetics. Part A, Vol.158A(4), pp.784-794
DOI: 10.1002/ajmg.a.35257
PMID: 22419666
PMCID: PMC3617127
NLM abbreviation: Am J Med Genet A
ISSN: 1552-4825
eISSN: 1552-4833
Grant note: Z99 ES999999 || ES / National Institute of Environmental Health Sciences : NIEHS
Language: English
Date published: 04/2012
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Orthopedics and Rehabilitation; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research; Internal Medicine
Record Identifier: 9984025366002771

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