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Genetic instrumental variable studies of effects of prenatal risk factors.

ABSTRACT: Identifying the effects of maternal risk factors during pregnancy on infant and child health is an area of tremendous research interest. However, policymakers are primarily interested in unraveling the causal effects of prenatal risk factors, not their associations with child health, which may be confounded by several unobserved factors. In this article, we evaluate the utility of genetic variants in three genes that have unequivocal evidence of being related to three major risk factors-CHRNA3 for smoking, ADH1B for alcohol use, and FTO for obesity-as instrumental variables for identifying the causal effects of such factors during pregnancy. Using two independent datasets, we find that these variants are overall predictive of the risk factors and are not systematically related to observed confounders, suggesting that they may be useful instruments. We also find some suggestive evidence that genetic effects are stronger during than before pregnancy. We provide an empirical example illustrating the use of these genetic variants as instruments to evaluate the effects of risk factors on birth weight. Finally, we offer suggestions for researchers contemplating the use of these variants as instruments.

SUBMITTER: Wehby GL

PROVIDER: S-EPMC3690512 | biostudies-literature | 2013

REPOSITORIES: biostudies-literature

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Genetic instrumental variable studies of effects of prenatal risk factors.

Wehby George L GL Scholder Stephanie von Hinke Kessler Sv

Biodemography and social biology 20130101 1

Identifying the effects of maternal risk factors during pregnancy on infant and child health is an area of tremendous research interest. However, policymakers are primarily interested in unraveling the causal effects of prenatal risk factors, not their associations with child health, which may be confounded by several unobserved factors. In this article, we evaluate the utility of genetic variants in three genes that have unequivocal evidence of being related to three major risk factors-CHRNA3 f ...[more]

PMID: 23701534

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Project description:OBJECTIVES:To assess the incremental effects of adding extra antihypertensive drugs from a new class to a patient's regimen. DESIGN:Instrumental variable analysis of data from SPRINT (Systolic Blood Pressure Intervention Trial). To account for confounding by indication-when treatments seem less effective if they are administered to sicker patients-randomization status was used as the instrumental variable. Patients' randomization status was either intensive (systolic blood pressure target <120 mm Hg) or standard (systolic blood pressure target <140 mm Hg) treatment. Results from instrumental variable models were compared with those from standard multivariable models. SETTING:Secondary data analysis of a randomized clinical trial conducted at 102 sites in 2010-15. PARTICIPANTS:9092 SPRINT participants with hypertension and increased cardiovascular risk but no history of diabetes or stroke. MAIN OUTCOMES MEASURES:Systolic blood pressure, major cardiovascular events, and serious adverse events. RESULTS:In standard multivariable models not adjusted for confounding by indication, addition of an antihypertensive drug from a new class was associated with modestly lower systolic blood pressure (-1.3 mm Hg, 95% confidence interval -1.6 to -1.0) and no change in major cardiovascular events (absolute risk of events per 1000 patient years, 0.5, 95% confidence interval -1.5 to 2.3). In instrumental variable models, the addition of an antihypertensive drug from a new class led to clinically important reductions in systolic blood pressure (-14.4 mm Hg, -15.6 to -13.3) and fewer major cardiovascular events (absolute risk -6.2, -10.9 to -1.3). Incremental reductions in systolic blood pressure remained large and similar in magnitude for patients already taking drugs from zero, one, two, or three or more drug classes. This finding was consistent across all subgroups of patients. The addition of another antihypertensive drug class was not associated with adverse events in either standard or instrumental variable models. CONCLUSIONS:After adjustment for confounding by indication, the addition of a new antihypertensive drug class led to large reductions in systolic blood pressure and major cardiovascular events among patients at high risk for cardiovascular events but without diabetes. Effects on systolic blood pressure persisted across all levels of baseline drug use and all subgroups of patients.

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Genetic instrumental variable studies of effects of prenatal risk factors.

Publications

Genetic instrumental variable studies of effects of prenatal risk factors.

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