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The Interplay between Maternal Smoking and Genes in Offspring Birth Weight

By Rita Dias Pereira, Cornelius A. Rietveld, Hans van Kippersluis

Posted 03 Nov 2020
medRxiv DOI: 10.1101/2020.10.30.20222844

It is well-established that both the childs genetic endowments as well as maternal smoking during pregnancy impact offspring birth weight. In this paper we move beyond the nature versus nurture debate by investigating the interaction between genetic endowments and this critical prenatal environmental exposure - maternal smoking - in determining birth weight. We draw on longitudinal data from the Avon Longitudinal Study of Parents and Children (ALSPAC) study and replicate our results using data from the UK Biobank. Genetic endowments of the children are proxied with a polygenic score that is constructed based on the results of the most recent genome-wide association study of birth weight. We instrument the maternal decision to smoke during pregnancy with a genetic variant (rs1051730) located in the nicotine receptor gene CHRNA3. This genetic variant is associated with the number of cigarettes consumed daily, and we present evidence that this is plausibly the only channel through which the maternal genetic variant affects the childs birth weight. Additionally, we deal with the misreporting of maternal smoking by using measures of cotinine, a biomarker of nicotine, collected from the mothers urine during their pregnancy. We confirm earlier findings that genetic endowments as well as maternal smoking during pregnancy significantly affects the childs birth weight. However, we do not find evidence of meaningful interactions between genetic endowments and an adverse fetal environment, suggesting that the childs genetic predisposition cannot cushion the damaging effects of maternal smoking.

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