Associations between brain structure and problematic alcohol use may reflect alcohol-induced toxicity and/or preexisting risk. Here, we applied a latent causal variable approach to genome-wide association study summary statistics of problematic alcohol use (n = 435,563) and magnetic resonance imaging-derived brain structure phenotypes (e.g., cortical volume, cortical thickness, white matter volume; ns ranging from 17,706 to 51,665) to test whether variability in brain structure may plausibly contribute to problematic alcohol use and/or whether problematic alcohol use influences brain structure. After correction for multiple testing within each modality, we find evidence that greater volume of the pars opercularis, greater thickness of the cuneus, and lower volume of the basal forebrain may plausibly contribute to problematic alcohol use. All other nominally-significant associations identify brain structure as a potential causal contributor to problematic alcohol use; there was no evidence suggesting that problematic alcohol use may cause differences in brain structure. Collectively, these results challenge common interpretations that associations between alcohol use and brain structure reflect consequences of alcohol, instead supporting emerging work suggesting that brain structure may reflect a predispositional risk factor for alcohol involvement.

大脑结构与有问题的饮酒之间的关联可能反映了酒精引起的毒性和/或先前存在的风险。在这里，我们将潜在因果变量方法应用于有问题的酒精使用 (n = 435,563) 和磁共振成像衍生的大脑结构表型（例如，皮质体积、皮质厚度、白质体积；ns 范围）的全基因组关联研究汇总统计从 17,706 到 51,665）来测试大脑结构的变异性是否可能导致有问题的饮酒和/或有问题的饮酒是否会影响大脑结构。在对每种模式中的多次测试进行校正后，我们发现有证据表明，更大的鳃盖部体积、更大的楔骨厚度和更小的基底前脑体积可能会导致饮酒问题。所有其他名义上重要的关联都将大脑结构确定为导致酗酒问题的潜在原因；没有证据表明有问题的饮酒会导致大脑结构的差异。总的来说，这些结果挑战了酒精使用与大脑结构之间的关联反映酒精后果的普遍解释，而不是支持表明大脑结构可能反映酒精参与的易感风险因素的新兴工作。