Journal article
Genome-wide interaction studies identify sex-specific risk alleles for nonsyndromic orofacial clefts
Genetic epidemiology, Vol.42(7), pp.664-672
10/2018
DOI: 10.1002/gepi.22158
PMCID: PMC6185762
PMID: 30277614
Abstract
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans and is notable for its apparent sexual dimorphism where approximately twice as many males are affected as females. The sources of this disparity are largely unknown, but interactions between genetic and sex effects are likely contributors. We examined gene-by-sex (G × S) interactions in a worldwide sample of 2,142 NSCL/P cases and 1,700 controls recruited from 13 countries. First, we performed genome-wide joint tests of the genetic (G) and G × S effects genome-wide using logistic regression assuming an additive genetic model and adjusting for 18 principal components of ancestry. We further interrogated loci with suggestive results from the joint test ( p < 1.00 × 10\n) by examining the G × S effects from the same model. Out of the 133 loci with suggestive results ( p < 1.00 × 10\n) for the joint test, we observed one genome-wide significant G × S effect in the 10q21 locus (rs72804706; p = 6.69 × 10\n; OR = 2.62 CI [1.89, 3.62]) and 16 suggestive G × S effects. At the intergenic 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. Our observation that the impact of genetic variants on NSCL/P risk differs for males and females may further our understanding of the genetic architecture of NSCL/P and the sex differences underlying clefts and other birth defects.
Details
- Title: Subtitle
- Genome-wide interaction studies identify sex-specific risk alleles for nonsyndromic orofacial clefts
- Creators
- Jenna C Carlson - Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PennsylvaniaNichole L Nidey - Department of Epidemiology, College of Public Health, University of Iowa, Iowa City, IowaAzeez Butali - Department of Oral Pathology, Radiology and Medicine, Dows Institute for Dental Research, College of Dentistry, University of Iowa, Iowa City, IowaCarmen J Buxo - Dental and Craniofacial Genomics Core, School of Dental Medicine, University of Puerto Rico, San Juan, Puerto RicoKaare Christensen - Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, DenmarkFrederic W-D Deleyiannis - Department of Surgery, Plastic and Reconstructive Surgery Division, University of Colorado School of Medicine, Denver, ColoradoJacqueline T Hecht - Department of Pediatrics, McGovern Medical School and School of Dentistry, UT Health at Houston, Houston, TexasL Leigh Field - Department of Medical Genetics, University of British Columbia, Vancouver, British Columbia, CanadaLina M Moreno-Uribe - Department of Orthodontics, College of Dentistry, University of Iowa, Iowa City, IowaIeda M Orioli - Department of Genetics, Institute of Biology, Federal University of Rio de Janeiro, Rio de Janeiro, BrazilFernando A Poletta - CEMIC-CONICET: Center for Medical Education and Clinical Research "Norberto Quirno", Buenos Aires, ArgentinaCarmencita Padilla - The Philippine Genome Center, University of the Philippines System, Manilla, PhilippinesAlexandre R Vieira - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniaSeth M Weinberg - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniaGeorge L Wehby - Department of Health Management and Policy, College of Public Health, University of Iowa, Iowa City, IowaEleanor Feingold - Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PennsylvaniaJeffrey C Murray - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IowaMary L Marazita - Department of Oral Biology, Center for Craniofacial and Dental Genetics, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniaElizabeth J Leslie - Department of Human Genetics, Emory University School of Medicine, Emory University, Atlanta, Georgia
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.42(7), pp.664-672
- DOI
- 10.1002/gepi.22158
- PMID
- 30277614
- PMCID
- PMC6185762
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Publisher
- United States
- Grant note
- R01-DE016148 / NIH HHS\nDE014667 / NIH HHS\nX01-HG007485 / NIH HHS\nR01 DE016148 / NIDCR NIH HHS\nR01 DE008559 / NIDCR NIH HHS\nMD001830 / NIH HHS\nU01-DE024425 / NIH HHS\nR01 DE011948 / NIDCR NIH HHS\nR01-DE011948 / NIH HHS\nU54 MD007587 / NIMHD NIH HHS\nR01 DE014667 / NIDCR NIH HHS\nDE011931 / NIH HHS\nHHSN268201200008I / NHLBI NIH HHS\nR01-DE014667 / NIH HHS\nR00-DE025060 / NIH HHS\nK99 DE024571 / NIDCR NIH HHS\nPICT-2016-3869 / Agencia Nacional de Promoción Científica y Tecnológica\nHHSN268201200008C / NHLBI NIH HHS\nR01 DE009886 / NIDCR NIH HHS\nS21 MD001830 / NIMHD NIH HHS\nDE016930 / NIH HHS\nR21 DE016930 / NIDCR NIH HHS\nR01 DD000295 / NCBDD CDC HHS\nDE008559 / NIH HHS\nDE012472 / NIH HHS\nR00 DE024571 / NIDCR NIH HHS\nDD000295 / NIH HHS\nDE009886 / NIH HHS\nR37 DE008559 / NIDCR NIH HHS\nK99-DE024571 / NIH HHS\nR00 DE025060 / NIDCR NIH HHS\nU54-MD007587 / NIH HHS\nHHSN268201200008I / Johns Hopkins Center for Inherited Disease Research\nU01 DE024425 / NIDCR NIH HHS\nR01 DE011931 / NIDCR NIH HHS
- Language
- English
- Date published
- 10/2018
- Academic Unit
- Preventive and Community Dentistry; Oral Pathology, Radiology and Medicine; Health Management and Policy; Addiction Medicine; Pediatric Dentistry; Craniofacial Anomalies Research Center; Orthodontics; Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Economics; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9984066099802771
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