Alcohol consumption and genetic risk for Alzheimer disease (AD) are among many factors known to be associated with brain structure in cognitively healthy adults. It is unclear, however, whether the effect of alcohol consumption on brain structure varies depending on a person's level of genetic risk for AD. We hypothesized that there is an interaction effect of alcohol consumption and a 33-SNP AD polygenic risk score (PRS) on the cortical thickness of brain regions known to be affected early in the course of AD. Studying 6,213 cognitively healthy subjects from the UK Biobank, we found a significant interaction effect of the 33-SNP AD PRS and alcohol consumption on this AD Cortical Thickness Signature. Stratified, among those who consume 12-24 g/day of alcohol, the 33-SNP AD PRS had a significant, positive association with AD Cortical Thickness Signature, with high-risk subjects having the greatest AD Cortical Thickness Signature. There were no significant associations of the 33-SNP AD PRS with AD Cortical Thickness Signature among the nondrinker or <1, 1-6, 6-12, 24-48, or >48 g/day groups. It is unclear whether this interaction is due to a detrimental or beneficial effect of moderate alcohol consumption in those with the highest genetic risk for AD.

中文翻译：

---

饮酒和阿尔茨海默病多基因风险评分对认知正常受试者大脑皮层厚度的交互作用。


已知与认知健康成年人的大脑结构相关的众多因素中，饮酒和阿尔茨海默病 (AD) 的遗传风险是其中之一。然而，目前尚不清楚饮酒对大脑结构的影响是否会根据一个人患 AD 的遗传风险水平而变化。我们假设饮酒和 33-SNP AD 多基因风险评分 (PRS) 对已知在 AD 病程早期受影响的大脑区域的皮质厚度存在相互作用。通过研究英国生物银行的 6,213 名认知健康受试者，我们发现 33-SNP AD PRS 和饮酒对 AD 皮质厚度特征有显着的交互作用。分层后，在每天饮酒 12-24 克的人群中，33-SNP AD PRS 与 AD 皮质厚度特征显着呈正相关，其中高风险受试者具有最大的 AD 皮质厚度特征。在非饮酒者或 <1、1-6、6-12、24-48 或 >48 g/天组中，33-SNP AD PRS 与 AD 皮质厚度特征没有显着相关性。目前尚不清楚这种相互作用是否是由于适度饮酒对 AD 遗传风险最高的人产生的有害或有益影响所致。