title: Genome wide study of maternal and parent-of-origin effects on the etiology of orofacial clefts.
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.
authors.affiliation: Biostatistics Branch, NIEHS/NIH, Durham, North Carolina, USA. shi2@niehs.nih.gov
authors.forename: Min
authors.initials: M
authors.lastname: Shi
authors.forename: Jeffrey C
authors.initials: JC
authors.lastname: Murray
authors.forename: Mary L
authors.initials: ML
authors.lastname: Marazita
authors.forename: Ronald G
authors.initials: RG
authors.lastname: Munger
authors.forename: Ingo
authors.initials: I
authors.lastname: Ruczinski
authors.forename: Jacqueline B
authors.initials: JB
authors.lastname: Hetmanski
authors.forename: Tao
authors.initials: T
authors.lastname: Wu
authors.forename: Tanda
authors.initials: T
authors.lastname: Murray
authors.forename: Richard J
authors.initials: RJ
authors.lastname: Redett
authors.forename: Allen J
authors.initials: AJ
authors.lastname: Wilcox
authors.forename: Rolv T
authors.initials: RT
authors.lastname: Lie
authors.forename: Ethylin Wang
authors.initials: EW
authors.lastname: Jabs
authors.forename: Yah Huei
authors.initials: YH
authors.lastname: Wu-Chou
authors.forename: Philip K
authors.initials: PK
authors.lastname: Chen
authors.forename: Hong
authors.initials: H
authors.lastname: Wang
authors.forename: Xiaoqian
authors.initials: X
authors.lastname: Ye
authors.forename: Vincent
authors.initials: V
authors.lastname: Yeow
authors.forename: Samuel S
authors.initials: SS
authors.lastname: Chong
authors.forename: Bing
authors.initials: B
authors.lastname: Shi
authors.forename: Kaare
authors.initials: K
authors.lastname: Christensen
authors.forename: Alan F
authors.initials: AF
authors.lastname: Scott
authors.forename: Poorav
authors.initials: P
authors.lastname: Patel
authors.forename: Felicia
authors.initials: F
authors.lastname: Cheah
authors.forename: Terri H
authors.initials: TH
authors.lastname: Beaty
mesh_terms: D002971:Cleft Lip / Q000209:etiology / Q000235:genetics*; D002972:Cleft Palate / Q000209:etiology / Q000235:genetics*; D015331:Cohort Studies; D019465:Craniofacial Abnormalities / Q000235:genetics*; D005260:Female; D016678:Genome; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008297:Male; D010290:Parents; D020641:Polymorphism, Single Nucleotide