CEMIC - CONICET   26185
CENTRO DE EDUCACION MEDICA E INVESTIGACIONES CLINICAS "NORBERTO QUIRNO"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Exploring the impact of sex-specific genetic effects on orofacial clefting.
Autor/es:
N. NIDEY; L. MORENO; F. POLETTA; S. WEINBERG; J. MURRAY; J. CARLSON; A. BUTALI; E. CASTILLA; A. VIEIRA; E. FEINGOLD; E. LESLIE; J. SHAFFER; I. ORIOLI; C. PADILLA; G. WEHBY; M. MARAZITA
Lugar:
Orlando
Reunión:
Congreso; American Society of Human Genetics 67 Annual Meeting; 2017
Institución organizadora:
American Society of Human Genetics
Resumen:
Non-syndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, affecting approximately 1 in 700 births worldwide. NSCL/P has complex etiology and heterogeneous phenotypic presentation including differences in prevalence by sex. Approximately twice as many males are affected with NSCL/P than females, and the source of this disparity is largely unknown. Interactions between genetic effects and sex effects have been hypothesized to help explain some of the differences seen in NSCL/P prevalence.To this end, we examined gene-by-sex interactions in a worldwide sample of 2142 NSCL/P cases and 1,700 controls recruited from 18 sites across 13 countries from North America, Central/South America, Asia, Europe and Africa. Joint tests of genetic and gene-by-sex effects were tested genome-wide (6,926,378 SNPs with MAF>0.05) using logistic regression assuming an additive genetic effect and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test (p < 1E-05) by examining the gene-by-sex effects from the same model.Suggestive results (p < 1E-05) for the joint test were observed in 133 loci. From these regions, one genome-wide significant gene-by-sex effect in the 10q21 locus (rs72804706; p=6.69E-09; OR=2.62[1.89, 3.62]) and 16 suggestive gene-by-sex effects were observed. At the 10q21 locus, the risk of NSCL/P is estimated to increase with additional copies of the minor allele for females, but the opposite effect for males. This locus lies within an intergenic region downstream of IPMK, whose impact on craniofacial development is unknown. Our observation that the impact of genetic variants on orofacial clefting risk differs for males and females at this locus may further our understanding of the genetic architecture of orofacial clefting and and the sex differences underlying clefts and some other birth defects. R01DE016148, X01HG007485, K99DE024571, R01-DE011931