Journal article
Evidence for SNP-SNP interaction identified through targeted sequencing of cleft case-parent trios
Genetic epidemiology, Vol.41(3), pp.244-250
04/2017
DOI: 10.1002/gepi.22023
PMCID: PMC5340569
PMID: 28019042
Abstract
Nonsyndromic cleft lip with or without cleft palate (NSCL/P) is the most common craniofacial birth defect in humans, affecting 1 in 700 live births. This malformation has a complex etiology where multiple genes and several environmental factors influence risk. At least a dozen different genes have been confirmed to be associated with risk of NSCL/P in previous studies. However, all the known genetic risk factors cannot fully explain the observed heritability of NSCL/P, and several authors have suggested gene-gene (G × G) interaction may be important in the etiology of this complex and heterogeneous malformation. We tested for G × G interactions using common single nucleotide polymorphic (SNP) markers from targeted sequencing in 13 regions identified by previous studies spanning 6.3 Mb of the genome in a study of 1,498 NSCL/P case-parent trios. We used the R-package trio to assess interactions between polymorphic markers in different genes, using a 1 degree of freedom (1df) test for screening, and a 4 degree of freedom (4df) test to assess statistical significance of epistatic interactions. To adjust for multiple comparisons, we performed permutation tests. The most significant interaction was observed between rs6029315 in MAFB and rs6681355 in IRF6 (4df P = 3.8 × 10
) in case-parent trios of European ancestry, which remained significant after correcting for multiple comparisons. However, no significant interaction was detected in trios of Asian ancestry.
Details
- Title: Subtitle
- Evidence for SNP-SNP interaction identified through targeted sequencing of cleft case-parent trios
- Creators
- Yanzi Xiao - Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, USAMargaret A Taub - Department of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USAIngo Ruczinski - Department of Biostatistics, School of Public Health, Johns Hopkins University, Baltimore, MD, USAFerdouse Begum - Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, USAJacqueline B Hetmanski - Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, USAHolger Schwender - Mathematical Institute, Heinrich Heine University, Düsseldorf, GermanyElizabeth J Leslie - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USADaniel C Koboldt - The Genome Institute, Washington University School of Medicine, St. Louis, MO, USAJeffrey C Murray - Department of Pediatrics, Carver College of Medicine, University of Iowa, Iowa City, IA, USAMary L Marazita - Center for Craniofacial and Dental Genetics, Department of Oral Biology, School of Dental Medicine, University of Pittsburgh, Pittsburgh, PA, USATerri H Beaty - Department of Epidemiology, School of Public Health, Johns Hopkins University, Baltimore, MD, USA
- Resource Type
- Journal article
- Publication Details
- Genetic epidemiology, Vol.41(3), pp.244-250
- DOI
- 10.1002/gepi.22023
- PMID
- 28019042
- PMCID
- PMC5340569
- NLM abbreviation
- Genet Epidemiol
- ISSN
- 0741-0395
- eISSN
- 1098-2272
- Publisher
- United States
- Grant note
- R01 DE014581 / NIDCR NIH HHS R01 DE016148 / NIDCR NIH HHS R01 DE008559 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS R21 DE016930 / NIDCR NIH HHS R00 DE025060 / NIDCR NIH HHS U01 DE018993 / NIDCR NIH HHS K99 DE025060 / NIDCR NIH HHS U01 HG005925 / NHGRI NIH HHS R01 DE009886 / NIDCR NIH HHS
- Language
- English
- Date published
- 04/2017
- Academic Unit
- Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
- Record Identifier
- 9984025446002771
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