Journal article
Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate
American journal of medical genetics. Part A, Vol.173(6), pp.1531-1538
06/2017
DOI: 10.1002/ajmg.a.38210
PMCID: PMC5444956
PMID: 28425186
Abstract
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is a group of common human birth defects with complex etiology. Although genome-wide association studies have successfully identified a number of risk loci, these loci only account for about 20% of the heritability of orofacial clefts. The "missing" heritability may be found in rare variants, copy number variants, or interactions. In this study, we investigated the role of low-frequency variants genotyped in 1995 cases and 1626 controls on the Illumina HumanCore + Exome chip. We performed two statistical tests, Sequence Kernel Association Test (SKAT) and Combined Multivariate and Collapsing (CMC) method using two minor allele frequency cutoffs (1% and 5%). We found that a burden of low-frequency coding variants in N4BP2, CDSN, PRTG, and AHRR were associated with increased risk of NSCL/P. Low-frequency variants in other genes were associated with decreased risk of NSCL/P. These results demonstrate that low-frequency variants contribute to the genetic etiology of NSCL/P.
Details
- Title: Subtitle
- Association studies of low-frequency coding variants in nonsyndromic cleft lip with or without cleft palate
- Creators
- Elizabeth J Leslie - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniaJenna C Carlson - Department of Biostatistics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PennsylvaniaJohn R Shaffer - Department of Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PennsylvaniaCarmen J Buxó - School of Dental Medicine, University of Puerto Rico, San Juan, Puerto RicoEduardo E Castilla - Laboratory of Congenital Malformation Epidemiology, Oswaldo Cruz Institute, FIOCRUZ, Rio de Janeiro, BrazilKaare Christensen - Department of Epidemiology, Institute of Public Health, University of Southern Denmark, Odense, DenmarkFrederic W B Deleyiannis - Department of Surgery, Plastic and Reconstructive Surgery, University of Colorado School of Medicine, Denver, ColoradoLeigh L Field - Department of Medical Genetics, University of British Columbia, Vancouver, CanadaJacqueline T Hecht - Department of Pediatrics, McGovern Medical School and School of Dentistry UT Health at Houston, Houston, TexasLina Moreno - 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, BrazilCarmencita Padilla - Philippine Genome Center, University of the Philippines System, Manila, The PhilippinesAlexandre R Vieira - Department of Human Genetics, Graduate School of Public Health, 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 Human Genetics, Graduate School of Public Health, University of Pittsburgh, Pittsburgh, PennsylvaniaSeth M Weinberg - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PennsylvaniaJeffrey C Murray - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IowaMary L Marazita - Clinical and Translational Science, School of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
- Resource Type
- Journal article
- Publication Details
- American journal of medical genetics. Part A, Vol.173(6), pp.1531-1538
- DOI
- 10.1002/ajmg.a.38210
- PMID
- 28425186
- PMCID
- PMC5444956
- NLM abbreviation
- Am J Med Genet A
- ISSN
- 1552-4825
- eISSN
- 1552-4833
- Publisher
- United States
- Grant note
- S21 MD001830 / NIMHD NIH HHS R01 DE016148 / NIDCR NIH HHS R21 DE016930 / NIDCR NIH HHS R01 DD000295 / NCBDD CDC HHS R01 DE011948 / NIDCR NIH HHS K99 DE025060 / NIDCR NIH HHS U54 MD007587 / NIMHD NIH HHS R01 DE014667 / NIDCR NIH HHS R25 MD007607 / NIMHD NIH HHS HHSN268201200008I / NHLBI NIH HHS R37 DE008559 / NIDCR NIH HHS R00 DE025060 / NIDCR NIH HHS K99 DE024571 / NIDCR NIH HHS HHSN268201200008C / NHLBI NIH HHS U01 DE024425 / NIDCR NIH HHS R01 DE009886 / NIDCR NIH HHS R01 DE011931 / NIDCR NIH HHS
- Language
- English
- Date published
- 06/2017
- Academic Unit
- Preventive and Community Dentistry; Orthodontics; Anatomy and Cell Biology; Health Management and Policy; Stead Family Department of Pediatrics; Epidemiology; Economics; Pediatric Dentistry; Craniofacial Anomalies Research Center; Public Policy Center (Archive); Dental Research
- Record Identifier
- 9984025309902771
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