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 ChristensenAlan F. Scott, Poorav Patel, Felicia Cheah, Terri H. Beaty

Research output: Contribution to journalArticlepeer-review

25 Scopus citations


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 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.

Original languageEnglish (US)
Pages (from-to)784-794
Number of pages11
JournalAmerican Journal of Medical Genetics, Part A
Volume158 A
Issue number4
StatePublished - Apr 2012


  • Association study
  • CL/P
  • CP
  • Family-based study
  • GWAS
  • Maternal genes
  • Parent-of-origin

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)


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