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 journalArticle

21 Citations (Scopus)

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

Original languageEnglish
Pages (from-to)784-794
Number of pages11
JournalAmerican Journal of Medical Genetics, Part A
Volume158 A
Issue number4
DOIs
Publication statusPublished - Apr 1 2012
Externally publishedYes

Fingerprint

Single Nucleotide Polymorphism
Mothers
Genome
Linear Models
Gene Regulatory Networks
Public Sector
Genome-Wide Association Study
Environmental Exposure
Denmark
Norway
Fathers
Sample Size
Haplotypes
Cohort Studies
Recurrence
Population

Keywords

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

ASJC Scopus subject areas

  • Genetics
  • Genetics(clinical)

Cite this

Shi, M., Murray, J. C., Marazita, M. L., Munger, R. G., Ruczinski, I., Hetmanski, J. B., ... Beaty, T. H. (2012). Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts. American Journal of Medical Genetics, Part A, 158 A(4), 784-794. https://doi.org/10.1002/ajmg.a.35257

Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts. / Shi, Min; Murray, Jeffrey C.; Marazita, Mary L.; Munger, Ronald G.; Ruczinski, Ingo; Hetmanski, Jacqueline B.; Wu, Tao; Murray, Tanda; Redett, Richard J.; Wilcox, Allen J.; Lie, Rolv T.; Jabs, Ethylin Wang; Wu-Chou, Yah Huei; Chen, Philip K.; Wang, Hong; Ye, Xiaoqian; Yeow, Vincent; Chong, Samuel S.; Shi, Bing; Christensen, Kaare; Scott, Alan F.; Patel, Poorav; Cheah, Felicia; Beaty, Terri H.

In: American Journal of Medical Genetics, Part A, Vol. 158 A, No. 4, 01.04.2012, p. 784-794.

Research output: Contribution to journalArticle

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', American Journal of Medical Genetics, Part A, vol. 158 A, no. 4, pp. 784-794. https://doi.org/10.1002/ajmg.a.35257
Shi, Min ; Murray, Jeffrey C. ; Marazita, Mary L. ; Munger, Ronald G. ; Ruczinski, Ingo ; Hetmanski, Jacqueline B. ; Wu, Tao ; Murray, Tanda ; Redett, Richard J. ; Wilcox, Allen J. ; Lie, Rolv T. ; Jabs, Ethylin Wang ; Wu-Chou, Yah Huei ; Chen, Philip K. ; Wang, Hong ; Ye, Xiaoqian ; Yeow, Vincent ; Chong, Samuel S. ; Shi, Bing ; Christensen, Kaare ; Scott, Alan F. ; Patel, Poorav ; Cheah, Felicia ; Beaty, Terri H. / Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts. In: American Journal of Medical Genetics, Part A. 2012 ; Vol. 158 A, No. 4. pp. 784-794.
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AU - Murray, Jeffrey C.

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AU - Munger, Ronald G.

AU - Ruczinski, Ingo

AU - Hetmanski, Jacqueline B.

AU - Wu, Tao

AU - Murray, Tanda

AU - Redett, Richard J.

AU - Wilcox, Allen J.

AU - Lie, Rolv T.

AU - Jabs, Ethylin Wang

AU - Wu-Chou, Yah Huei

AU - Chen, Philip K.

AU - Wang, Hong

AU - Ye, Xiaoqian

AU - Yeow, Vincent

AU - Chong, Samuel S.

AU - Shi, Bing

AU - Christensen, Kaare

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