Genome-wide association studies of substance-use disorders, including problematic tobacco, alcohol, cannabis and opioid use, have provided evidence for a component of genetic liability that is shared across these traits. To explore this shared liability, Hatoum et al. performed multivariate genome-wide association analyses combining datasets for problematic alcohol use, problematic tobacco use, cannabis use disorder, and opioid use disorder in a total sample size of over 1 million individuals. They found that a general addiction risk factor, defined using genomic structural equation modeling, was associated with 17 independent loci at genome-wide significance. Gene-based analyses further identified associations with 42 genes, including FTO, DRD2 and PDE4B, while linkage disequilibrium score regression analyses identified positive genetic correlations with several traits, including suicide attempt, self-medication for anxiety or depression, and externalizing behaviors. In a follow-up study of 4,491 substance-naive children, a polygenic score for the general addiction risk factor was positively correlated with several traits, including childhood externalizing behaviors, thought problems, sleep duration, and family history of substance abuse and mental illness. These analyses provide clues into the biological pathways that influence substance-use disorders and their relationship with other behavioral traits.

物质使用障碍的全基因组关联研究，包括有问题的烟草、酒精、大麻和阿片类药物的使用，为这些特征共有的遗传责任组成部分提供了证据。为了探索这种共同责任，Hatoum 等人。对超过 100 万人的总样本量进行了多变量全基因组关联分析，结合了有问题的酒精使用、有问题的烟草使用、大麻使用障碍和阿片类药物使用障碍的数据集。他们发现，使用基因组结构方程模型定义的一般成瘾风险因素与 17 个具有全基因组意义的独立位点相关。基于基因的分析进一步确定了与 42 个基因的关联，包括FTO、DRD2和PDE4B，而连锁不平衡评分回归分析确定了与几种特征的正遗传相关性，包括自杀未遂、焦虑或抑郁的自我药物治疗以及外化行为。在对 4,491 名未接触过药物的儿童进行的后续研究中，一般成瘾风险因素的多基因评分与多种特征呈正相关，包括儿童外化行为、思维问题、睡眠时间以及药物滥用和精神疾病的家族史。这些分析为影响物质使用障碍的生物学途径及其与其他行为特征的关系提供了线索。