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

Genome wide study of maternal and parent‐of‐origin effects on the etiology of orofacial clefts We performed a genome wide association analysis of maternally‐mediated genetic effects and parent‐of‐origin (POO) effects on risk of orofacial clefting (OC) 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 POO effects play major roles in the etiology of OC 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 POO 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. Published 2012. This article is a U.S. Government work and is in the public domain in the USA. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png American Journal of Medical Genetics Part A Wiley

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

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References (36)

Publisher
Wiley
Copyright
Copyright © 2012 Wiley Subscription Services, Inc., A Wiley Company
ISSN
1552-4825
eISSN
1552-4833
DOI
10.1002/ajmg.a.35257
pmid
22419666
Publisher site
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Abstract

We performed a genome wide association analysis of maternally‐mediated genetic effects and parent‐of‐origin (POO) effects on risk of orofacial clefting (OC) 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 POO effects play major roles in the etiology of OC 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 POO 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. Published 2012. This article is a U.S. Government work and is in the public domain in the USA.

Journal

American Journal of Medical Genetics Part A – Wiley

Published: Apr 1, 2012

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