Crick Daisy C P, Medland Sarah E, Smith George Davey, Evans David M
Institute for Molecular Bioscience, The University of Queensland, Brisbane, QLD, 4072, Australia.
QIMR Berghofer Medical Research Institute, Herston, QLD, Australia.
Behav Genet. 2025 Jul 16. doi: 10.1007/s10519-025-10226-0.
Hand preference first appears in early development, yet twin studies and GWAS show that only a minority of variance is explained by heritable genetic factors. Using UK Biobank data and multivariable logistic regression to test associations between potential causes of handedness and offspring hand preference, we then investigated the potential causal effect of maternal smoking during pregnancy on offspring handedness using a proxy gene-by-environment (GxE) Mendelian randomization design. We used rs16969968 in the CHRNA5 gene and a polygenic risk score of genome-wide significant smoking-heaviness variants to proxy smoking behaviour. We stratified based on reported maternal smoking during pregnancy because, regardless of genotype, any causal effect of maternal smoking heaviness on offspring handedness should only manifest in individuals whose mothers smoked during pregnancy. Using traditional epidemiological methods, we found maternal smoking during pregnancy increased the probability of being right-handed after adjustment for covariates. Despite this, when using the GxE MR analyses we found no strong causal effect of maternal smoking during pregnancy on offspring hand-preference. Our findings using the UK Biobank cohort align with previous findings and emphasise the impact of factors such as birth year, birthweight, being part of a multiple birth and breastfeeding on hand preference. However, we found no strong evidence for a causal link between maternal smoking and offspring handedness. The main factors contributing to variation in hand preference remain unresolved.
利手现象最早出现在早期发育阶段，但双胞胎研究和全基因组关联研究表明，只有少数差异可由遗传因素解释。我们利用英国生物银行的数据和多变量逻辑回归来测试利手潜在成因与后代利手之间的关联，然后使用代理基因-环境（GxE）孟德尔随机化设计，研究孕期母亲吸烟对后代利手的潜在因果效应。我们使用CHRNA5基因中的rs16969968以及全基因组显著的吸烟重度变异的多基因风险评分来代表吸烟行为。我们根据报告的孕期母亲吸烟情况进行分层，因为无论基因型如何，母亲吸烟重度对后代利手的任何因果效应都应仅在其母亲孕期吸烟的个体中表现出来。使用传统流行病学方法，我们发现调整协变量后，孕期母亲吸烟会增加后代惯用右手的概率。尽管如此，在使用GxE孟德尔随机化分析时，我们发现孕期母亲吸烟对后代利手没有强烈的因果效应。我们使用英国生物银行队列得出的研究结果与之前的研究结果一致，并强调了出生年份、出生体重、多胞胎以及母乳喂养等因素对利手的影响。然而，我们没有发现有力证据表明母亲吸烟与后代利手之间存在因果联系。导致利手差异的主要因素仍未得到解决。
