Conflict of interest: None.
Article first published online: 14 MAR 2012
Published 2012 Wiley Periodicals, Inc. This article is a U.S. Government work and is in the public domain in the USA.
American Journal of Medical Genetics Part A
Volume 158A, Issue 4, pages 784–794, April 2012
How to Cite
Shi, M., Murray, J. C., Marazita, M. L., Munger, R. G., Ruczinski, I., Hetmanski, J. B., Wu, T., Murray, T., Redett, R. J., Wilcox, A. J., Lie, R. T., Jabs, E. W., Wu-Chou, Y. H., Chen, P. K., Wang, H., Ye, X., Yeow, V., Chong, S. S., Shi, B., Christensen, K., Scott, A. F., Patel, P., Cheah, F. and Beaty, T. H. (2012), Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts. Am. J. Med. Genet., 158A: 784–794. doi: 10.1002/ajmg.a.35257
How to Cite this Article: Shi M, Murray JC, Marazita ML, Munger RG, Ruczinski I, Hetmanski JB, Wu T, Murray T, Redett RJ, Wilcox AJ, Lie RT, Jabs EW, Wu-Chou, YH, Chen PK, Wang H, Ye X, Yeow V, Chong SS, Shi B, Christensen K, Scott AF, Patel P, Cheah F, Beaty TH. 2012. Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts. Am J Med Genet Part A 158A:784–794.
- Issue published online: 23 MAR 2012
- Article first published online: 14 MAR 2012
- Manuscript Accepted: 19 DEC 2011
- Manuscript Received: 11 AUG 2011
- National Institute for Dental and Craniofacial Research. Grant Number: U01-DE-018993
- National Institute of Dental & Craniofacial Research. Grant Numbers: R21-DE-013707, R37-DE-08559, R01-DE-014581
- maternal genes;
- family-based study;
- association study
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.