Pereira Rita Dias, Rietveld Cornelius A, van Kippersluis Hans
Erasmus School of Economics, Erasmus University Rotterdam.
Tinbergen Institute.
medRxiv. 2020 Nov 3:2020.10.30.20222844. doi: 10.1101/2020.10.30.20222844.
It is well-established that both the child's genetic endowments as well as maternal smoking during pregnancy impact offspring birth weight. In this paper we move beyond the nature 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 child's birth weight. Additionally, we deal with the misreporting of maternal smoking by using measures of cotinine, a biomarker of nicotine, collected from the mother's urine during their pregnancy. We confirm earlier findings that genetic endowments as well as maternal smoking during pregnancy significantly affects the child's birth weight. However, we do not find evidence of meaningful interactions between genetic endowments and an adverse fetal environment, suggesting that the child's genetic predisposition cannot cushion the damaging effects of maternal smoking.
众所周知，儿童的遗传禀赋以及孕期母亲吸烟都会影响后代的出生体重。在本文中，我们通过研究遗传禀赋与这一关键的产前环境暴露因素——母亲吸烟——在决定出生体重方面的相互作用，超越了先天与后天的争论。我们利用来自阿冯父母与儿童纵向研究（ALSPAC）的纵向数据，并使用英国生物银行的数据来复制我们的结果。儿童的遗传禀赋用一个多基因分数来代理，该分数是根据最近关于出生体重的全基因组关联研究结果构建的。我们用位于尼古丁受体基因CHRNA3中的一个基因变异（rs1051730）来作为母亲孕期吸烟决定的工具变量。这个基因变异与每日吸烟量有关，并且我们提供的证据表明这可能是母亲基因变异影响孩子出生体重的唯一途径。此外，我们通过使用从母亲孕期尿液中收集的可替宁（一种尼古丁生物标志物）测量值来处理母亲吸烟情况的误报问题。我们证实了早期的研究结果，即遗传禀赋以及孕期母亲吸烟会显著影响孩子的出生体重。然而，我们没有发现遗传禀赋与不良胎儿环境之间存在有意义的相互作用的证据，这表明儿童的遗传易感性无法缓冲母亲吸烟的有害影响。
