Interaction effect of alcohol consumption and Alzheimer disease polygenic risk score on the brain cortical thickness of cognitively normal subjects

Abstract

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.

Keywords: Alzheimer disease; ApoE-4; UK Biobank; alcohol; cortical thickness; neuroimaging.