Assessing the impact of nicotine dependence genes on the risk of facial clefts: An example of the use of national registry and biobank data

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

doi:10.5324/nje.v21i2.1500

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Assessing the impact of nicotine dependence genes on the risk of facial clefts: An example of the use of national registry and biobank data

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Assessing the impact of nicotine dependence genes on the risk of facial clefts: An example of the use of national registry and biobank data

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

Norsk epidemiologi, Vol.21(2), pp.241-250

2012

DOI: 10.5324/nje.v21i2.1500

PMCID: PMC4594948

PMID: 26451072

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Abstract

Maternal smoking during pregnancy has been associated with risk of facial clefts in offspring, but causation has not yet been established. It is possible that the effect of maternal smoking on facial clefts is mediated through genes that are involved in nicotine dependence. Gamma-aminobutyric acid B receptor 2 ( ), dopa decarboxylase ( ), and cholinergic receptor nicotinic alpha 4 ( ) are three examples of genes that have previously shown strong associations with nicotine dependence. We used a population-based sample of 377 case-parent trios of cleft lip with or without cleft palate (CL/P) and 762 control-parent trios from Norway (1996-2001) to investigate whether variants in and are associated with maternal first-trimester smoking and with clefting risk. We used HAPLIN (Gjessing et al. 2006), a statistical software tailored for family-based association tests, to perform haplotype-based analyses on 12 SNPs in these genes (rs10985765, rs1435252, rs3780422, rs2779562, and rs3750344 in ; rs2060762, rs3757472, rs1451371, rs3735273, and rs921451 in ; rs4522666 and rs1044393 in ). When analyzed one at a time, there was little evidence of association between any of the 12 SNPs and maternal first-trimester smoking. In haplotype analyses, however, one copy of the maternal G-G-c-G-c haplotype in was linked with smoking prevalence (odds ratio: 1.5; 95% confidence interval: 1.0-2.1). This same haplotype also increased the risk of isolated CL/P in offspring by 1.5-fold with one copy and 2.4-fold with two copies ( = 0.06). No statistically significant associations were detected with and . Despite strong associations previously reported between nicotine dependence and variants in , and , these genes were poor predictors of maternal first-trimester smoking in our data. The direct association of the haplotype with CL/P suggests that this haplotype may either have direct effects on clefts or it may influence clefting risks through other yet unexplored risk behavior(s).

cleft palate

Cleft lip

nicotine dependence

smoking

Details

Title: Subtitle: Assessing the impact of nicotine dependence genes on the risk of facial clefts: An example of the use of national registry and biobank data
Creators: Astanand Jugessur - Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway ; Craniofacial Research, Murdoch Childrens Research Institute, Royal Children's Hospital, Parkville, Victoria, Australia
Allen J Wilcox - Epidemiology Branch, National Institute of Environmental Health Sciences (NIEHS), Research Triangle Park, Durham, North Carolina, USA
Jeffrey C Murray - Departments of Pediatrics, Epidemiology and Biological Sciences, University of Iowa, Iowa City, Iowa, USA
Håkon K Gjessing - Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway ; 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
Roy M Nilsen - Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway
Rolv T Lie - Department of Public Health and Primary Health Care, University of Bergen, Bergen, Norway ; Medical Birth Registry of Norway, Norwegian Institute of Public Health, Bergen, Norway
Resource Type: Journal article
Publication Details: Norsk epidemiologi, Vol.21(2), pp.241-250
DOI: 10.5324/nje.v21i2.1500
PMID: 26451072
PMCID: PMC4594948
NLM abbreviation: Nor Epidemiol
ISSN: 0803-2491
eISSN: 1891-5477
Publisher: Norway
Grant note: R37 DE008559 / NIDCR NIH HHS R01 DE008559 / NIDCR NIH HHS ZIA ES049027-16 / Intramural NIH HHS
Language: English
Date published: 2012
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984025562002771

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