Genetic Variants in IRF6 and the Risk of Facial Clefts: Single-Marker and Haplotype-Based Analyses in a Population-Based Case-Control Study of Facial Clefts in Norway

Astanand Jugessur; Fedik Rahimov; Rolv T Lie; Allen J Wilcox; Håkon K Gjessing; Roy M Nilsen; Truc Trung Nguyen; Jeffrey C Murray

doi:10.1002/gepi.20314

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Genetic Variants in IRF6 and the Risk of Facial Clefts: Single-Marker and Haplotype-Based Analyses in a Population-Based Case-Control Study of Facial Clefts in Norway

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Genetic Variants in IRF6 and the Risk of Facial Clefts: Single-Marker and Haplotype-Based Analyses in a Population-Based Case-Control Study of Facial Clefts in Norway

Astanand Jugessur, Fedik Rahimov, Rolv T Lie, Allen J Wilcox, Håkon K Gjessing, Roy M Nilsen, Truc Trung Nguyen and Jeffrey C Murray

Genetic epidemiology, Vol.32(5), pp.413-424

07/2008

DOI: 10.1002/gepi.20314

PMCID: PMC2680842

PMID: 18278815

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https://www.ncbi.nlm.nih.gov/pmc/articles/2680842View

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Abstract

Mutations in the gene encoding interferon regulatory factor 6 ( IRF6 ) underlie a common form of syndromic clefting known as Van der Woude syndrome. Lip pits and missing teeth are the only additional features distinguishing the syndrome from isolated clefts. Van der Woude syndrome, therefore, provides an excellent model for studying the isolated forms of clefting. From a population-based case-control study of facial clefts in Norway (1996–2001), we selected 377 cleft lip with or without cleft palate (CL/P), 196 cleft palate only (CPO), and 763 control infant-parent triads for analysis. We genotyped six single nucleotide polymorphisms within the IRF6 locus and estimated the relative risks (RR) conferred on the child by alleles and haplotypes of the child and of the mother. On the whole, there were strong statistical associations with CL/P but not CPO in our data. In single-marker analyses, mothers with a double-dose of the ‘a’-allele at rs4844880 had an increased risk of having a child with CL/P (RR = 1.85, 95% confidence interval: 1.04–3.25; P = 0.036). An RR of 0.38 (95% confidence interval: 0.16–0.92; P = 0.031) was obtained when the child carried a single-dose of the ‘a’-allele at rs2235371 (the p.V274I polymorphism). The P -value for the overall test was <0.001. In haplotype analyses, several of the fetal and maternal haplotype relative risks were statistically significant individually but were not strong enough to show up on the overall test ( P = 0.113). Taken together, these findings further support a role for IRF6 variants in clefting of the lip and provide specific risk estimates in a Norwegian population.

haplotype analysis

log-linear model

HapMap

case-control

association analysis

haplotype relative risk

facial clefts

IRF6

HAPLIN

birth defects

genetic epidemiology

case-parent triad

Details

Title: Subtitle: Genetic Variants in IRF6 and the Risk of Facial Clefts: Single-Marker and Haplotype-Based Analyses in a Population-Based Case-Control Study of Facial Clefts in Norway
Creators: Astanand Jugessur - Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
Fedik Rahimov - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Rolv T Lie - Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
Allen J Wilcox - National Institute of Environmental Health Sciences, Research Triangle Park, Durham, North Carolina
Håkon K Gjessing - Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
Roy M Nilsen - Section for Epidemiology and Medical Statistics, Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway
Truc Trung Nguyen - Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway
Jeffrey C Murray - Department of Pediatrics, University of Iowa, Iowa City, Iowa
Resource Type: Journal article
Publication Details: Genetic epidemiology, Vol.32(5), pp.413-424
DOI: 10.1002/gepi.20314
PMID: 18278815
PMCID: PMC2680842
NLM abbreviation: Genet Epidemiol
ISSN: 0741-0395
eISSN: 1098-2272
Language: English
Date published: 07/2008
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984025359702771

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