Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts

Oivind Skare; Astanand Jugessur; Rolv Terje Lie; Allen James Wilcox; Jeffrey Clark Murray; Astrid Lunde; Truc Trung Nguyen; Håkon Kristian Gjessing

doi:10.1111/j.1469-1809.2012.00707.x

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Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts

Journal article

Peer reviewed

Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts

Oivind Skare, Astanand Jugessur, Rolv Terje Lie, Allen James Wilcox, Jeffrey Clark Murray, Astrid Lunde, Truc Trung Nguyen and Håkon Kristian Gjessing

Annals of human genetics, Vol.76(3), pp.221-236

05/2012

DOI: 10.1111/j.1469-1809.2012.00707.x

PMCID: PMC3334353

PMID: 22497478

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Abstract

Orofacial clefts are common birth defects with strong evidence for both genetic and environmental causal factors. Candidate gene studies combined with exposures known to influence the outcome provide a highly targeted approach to detecting GxE interactions. We developed a new statistical approach that combines the case-control and offspring-parent triad designs into a "hybrid design" to search for GxE interactions among 334 autosomal cleft candidate genes and maternal first-trimester exposure to smoking, alcohol, coffee, folic acid supplements, dietary folate and vitamin A. The study population comprised 425 case-parent triads of isolated clefts and 562 control-parent triads derived from a nationwide study of orofacial clefts in Norway (1996-2001). A full maximum-likelihood model was used in combination with a Wald test statistic to screen for statistically significant GxE interaction between strata of exposed and unexposed mothers. In addition, we performed pathway-based analyses on 28 detoxification genes and 21 genes involved in folic acid metabolism. With the possible exception of the T-box 4 gene (TBX4) and dietary folate interaction in isolated CPO, there was little evidence overall of GxE interaction in our data. This study is the largest to date aimed at detecting interactions between orofacial clefts candidate genes and well-established risk exposures.

Coffee

Pregnancy

Humans

Smoking - genetics

Cleft Palate - genetics

Vitamin A - genetics

Gene-Environment Interaction

Maternal Exposure

Alcohol Drinking - genetics

Case-Control Studies

Cleft Lip - genetics

Folic Acid - metabolism

Female

Dietary Supplements

Research Design

Details

Title: Subtitle: Application of a novel hybrid study design to explore gene-environment interactions in orofacial clefts
Creators: Oivind Skare - Division of Epidemiology, Norwegian Institute of Public Health, Oslo, Norway. oivind.skare@medisin.uio.no
Astanand Jugessur
Rolv Terje Lie
Allen James Wilcox
Jeffrey Clark Murray
Astrid Lunde
Truc Trung Nguyen
Håkon Kristian Gjessing
Resource Type: Journal article
Publication Details: Annals of human genetics, Vol.76(3), pp.221-236
DOI: 10.1111/j.1469-1809.2012.00707.x
PMID: 22497478
PMCID: PMC3334353
NLM abbreviation: Ann Hum Genet
ISSN: 0003-4800
eISSN: 1469-1809
Publisher: England
Grant note: P30 ES005605 / NIEHS NIH HHS R01 DE011948-04 / NIDCR NIH HHS R01 DE008559-10 / NIDCR NIH HHS P60 DE013076-01 / NIDCR NIH HHS R01 DE008559 / NIDCR NIH HHS P30 ES05605 / NIEHS NIH HHS R01 DE011948 / NIDCR NIH HHS N01 HG065403 / NHGRI NIH HHS P60 DE013076 / NIDCR NIH HHS N01HG65403 / NHGRI NIH HHS P30 ES005605-11 / NIEHS NIH HHS Intramural NIH HHS P60 DE13076 / NIDCR NIH HHS R37 DE008559 / NIDCR NIH HHS DE08559 / NIDCR NIH HHS R01 DE-11948-04 / NIDCR NIH HHS
Language: English
Date published: 05/2012
Academic Unit: Anatomy and Cell Biology; Stead Family Department of Pediatrics; Epidemiology; Pediatric Dentistry; Craniofacial Anomalies Research Center; Dental Research
Record Identifier: 9984025480802771

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