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Application of a Novel Hybrid Study Design to Explore Gene‐Environment Interactions in Orofacial Clefts

Application of a Novel Hybrid Study Design to Explore Gene‐Environment Interactions in Orofacial... 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. http://www.deepdyve.com/assets/images/DeepDyve-Logo-lg.png Annals of Human Genetics Wiley

Application of a Novel Hybrid Study Design to Explore Gene‐Environment Interactions in Orofacial Clefts

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References (56)

Publisher
Wiley
Copyright
Copyright © 2012 Wiley Subscription Services
ISSN
0003-4800
eISSN
1469-1809
DOI
10.1111/j.1469-1809.2012.00707.x
pmid
22497478
Publisher site
See Article on Publisher Site

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.

Journal

Annals of Human GeneticsWiley

Published: Jan 1, 2012

Keywords: ; ; ; ;

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