Dataset Information

GENES AS INSTRUMENTS FOR STUDYING RISK BEHAVIOR EFFECTS: AN APPLICATION TO MATERNAL SMOKING AND OROFACIAL CLEFTS.

ABSTRACT: This study uses instrumental variable (IV) models with genetic instruments to assess the effects of maternal smoking on the child's risk of orofacial clefts (OFC), a common birth defect. The study uses genotypic variants in neurotransmitter and detoxification genes relateded to smoking as instruments for cigarette smoking before and during pregnancy. Conditional maximum likelihood and two-stage IV probit models are used to estimate the IV model. The data are from a population-level sample of affected and unaffected children in Norway. The selected genetic instruments generally fit the IV assumptions but may be considered "weak" in predicting cigarette smoking. We find that smoking before and during pregnancy increases OFC risk substantially under the IV model (by about 4-5 times at the sample average smoking rate). This effect is greater than that found with classical analytic models. This may be because the usual models are not able to consider self-selection into smoking based on unobserved confounders, or it may to some degree reflect limitations of the instruments. Inference based on weak-instrument robust confidence bounds is consistent with standard inference. Genetic instruments may provide a valuable approach to estimate the "causal" effects of risk behaviors with genetic-predisposing factors (such as smoking) on health and socioeconomic outcomes.

SUBMITTER: Wehby G

PROVIDER: S-EPMC3216039 | biostudies-literature | 2011 Jul

REPOSITORIES: biostudies-literature

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GENES AS INSTRUMENTS FOR STUDYING RISK BEHAVIOR EFFECTS: AN APPLICATION TO MATERNAL SMOKING AND OROFACIAL CLEFTS.

Wehby George G Jugessur Astanand A Murray Jeffrey C JC Moreno Lina L Wilcox Allen A Lie Rolv T RT

Health services & outcomes research methodology 20110701 1-2

This study uses instrumental variable (IV) models with genetic instruments to assess the effects of maternal smoking on the child's risk of orofacial clefts (OFC), a common birth defect. The study uses genotypic variants in neurotransmitter and detoxification genes relateded to smoking as instruments for cigarette smoking before and during pregnancy. Conditional maximum likelihood and two-stage IV probit models are used to estimate the IV model. The data are from a population-level sample of aff ...[more]

PMID: 22102793

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Project description:BackgroundStudies have found a consistent positive association between maternal smoking and non-syndromic orofacial clefts (NSOFC). However, no comprehensive assessment of the association between NSOFC and passive smoking has been undertaken. This systematic review and meta-analysis explores the relationship between maternal passive smoking and NSOFC, and compares the associations between passive and active smoking.Methods and findingsSearch strategy, inclusion / exclusion criteria, and data extraction from studies reporting maternal passive smoking and NSOFC was implemented without language restrictions. Risks of bias in the identified studies were assessed and this information was used in sensitivity analyses to explain heterogeneity. Meta-analysis and meta-regression of the extracted data were performed. Egger's test was used to test for small study effects. Fourteen eligible articles were identified. Maternal passive smoking exposure was associated with a twofold increase in risk of NSOFC (odds ratio: 2.11, 95% confidence interval: 1.54-2.89); this was apparent for both cleft lip with and without palate (OR: 2.05, 95% CI: 1.27-3.3) and cleft palate (OR: 2.11, 95% CI: 1.23-3.62). There was substantial heterogeneity between studies. In the studies that provided data enabling crude and adjusted odd ratios to be compared, adjustment for potential confounders attenuated the magnitude of association to about a 1.5-fold increase in risk.ConclusionOverall, maternal passive smoking exposure results in a 1.5 fold increase in risk of NSOFC, similar to the magnitude of risk reported for active smoking, but there is marked heterogeneity between studies. This heterogeneity is not explained by differences in the distribution of cleft types, adjustment for covariates, broad geographic region, or study bias/quality. This thorough meta-analysis provides further evidence to minimize exposure to environmental tobacco smoke in policy making fora and in health promotion initiatives.

Dataset Information

GENES AS INSTRUMENTS FOR STUDYING RISK BEHAVIOR EFFECTS: AN APPLICATION TO MATERNAL SMOKING AND OROFACIAL CLEFTS.

Publications

GENES AS INSTRUMENTS FOR STUDYING RISK BEHAVIOR EFFECTS: AN APPLICATION TO MATERNAL SMOKING AND OROFACIAL CLEFTS.

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