Wormington Briar, Thorp Jackson G, Gerring Zachary F, Scott James G, Akosile Wole, Derks Eske M
Translational Neurogenomics Laboratory, QIMR Berghofer, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
Translational Neurogenomics Laboratory, QIMR Berghofer, Brisbane, Australia; Faculty of Medicine, University of Queensland, Brisbane, Australia.
Psychiatry Res. 2024 Dec;342:116200. doi: 10.1016/j.psychres.2024.116200. Epub 2024 Sep 16.
Although harmful substance use is common and represented by shared symptom features and high genetic correlations, the underlying genetic relationships between substance use traits have not been fully explored. We have investigated the genetic architecture of substance use traits through exploratory and confirmatory factor analyses using genomic structural equation modeling (Genomic SEM), and explored genetic correlations between different aspects of substance use and mental health-related traits. Genomic SEM was used to identify latent factors representing the relationships between 14 substance use traits (alcohol, nicotine, cannabis and opioid use), and to confirm or modify existing latent factors for 38 mental health-related traits. A bi-factor model best explained the genetic overlap between substance use traits, including a general substance use factor and two sub-factors representing genetic liability specific to alcohol use or smoking. The SNP-based heritability of these factors ranged from 2 to 7 % and each factor had 10 or more independent significant SNPs identified. Bivariate correlations revealed patterns of genetic overlap with other mental health-related factors unique to each substance use factor. Variations in the genetic overlap between psychiatric traits and different aspects of substance use can be used to further investigate the pleiotropy present between these traits, and explore commonalities in etiology.
尽管有害物质使用很常见，且具有共同的症状特征和高度的遗传相关性，但物质使用性状之间潜在的遗传关系尚未得到充分探索。我们通过使用基因组结构方程模型（Genomic SEM）进行探索性和验证性因子分析，研究了物质使用性状的遗传结构，并探讨了物质使用不同方面与心理健康相关性状之间的遗传相关性。Genomic SEM用于识别代表14种物质使用性状（酒精、尼古丁、大麻和阿片类药物使用）之间关系的潜在因子，并确认或修改38种心理健康相关性状的现有潜在因子。双因素模型最能解释物质使用性状之间的遗传重叠，包括一个一般物质使用因子和两个分别代表酒精使用或吸烟特定遗传易感性的子因子。这些因子基于单核苷酸多态性（SNP）的遗传力范围为2%至7%，且每个因子都有10个或更多独立的显著SNP被识别出来。双变量相关性揭示了与每个物质使用因子特有的其他心理健康相关因子的遗传重叠模式。精神疾病性状与物质使用不同方面之间遗传重叠的变化可用于进一步研究这些性状之间存在的多效性，并探索病因学上的共性。
