Measuring the Associations Between Brain Morphometry and Polygenic Risk Scores for Substance use Disorders in Drug-Naive Adolescents.

IF 2.2 4区 医学 Q2 BEHAVIORAL SCIENCES
Sydney Kramer, Mei-Hsin Su, Mallory Stephenson, Jill Rabinowitz, Brion Maher, Roxann Roberson-Nay, Luis F S Castro-de-Araujo, Yi Zhou, Michael C Neale, Nathan A Gillespie
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Abstract

Substance use has been associated with differences in adult brain morphology; however, it is unclear whether these differences precede or are a result of substance use substance use. We investigated the impact of polygenic risk scores (PRSs) for cannabis use disorder (CUD) and general substance use and substance use disorder liability (SU/SUD) on brain morphology in drug-naïve adolescents. Baseline data were used from 1874 European-descent participants (ages 9-11) comprising 222, 328 and 387 pairs of MZ twins, DZ twins, and Non-Twin Siblings, respectively, in the Adolescent Brain Cognitive Development Study. We fitted multivariate twin models to estimate the putative effects of CUD, SU/SUD, and brain region-specific PRSs. These models assessed their influence on six subcortical and two cortical phenotypes. PRS for CUD and SU/SUD were created based on GWAS conducted by Johnson et al. (Lancet Psychiatry 7:1032, 2020) and Hatoum et al. (Nat Ment Health 1:210-223, 2023), respectively. When decomposing variance in each brain region of interest (ROI), we used the corresponding ROI-specific PRS. Brain morphometry in drug-naive subjects was unrelated to CUD PRS. The variance explained in each ROI by its corresponding PRS ranged from 0.8 to 4.4%. The SU/SUD PRS showed marginally significant effects (0.2-0.4%) on cortical surface area and nucleus accumbens volume, but overall effect sizes were small. This study failed to reject the null hypothesis of no association between genetic risk for substance use and brain morphometry among baseline drug-naive adolescents. Genetic risk for CUD was not associated with brain morphometry among drug-naive adolescents, but a weak association with general addiction and substance use risk (SU/SUD) particularly in nucleus accumbens volume and total cortical surface area, was observed.

测量未吸毒青少年物质使用障碍的脑形态测量和多基因风险评分之间的关系。
药物使用与成人大脑形态的差异有关;然而,尚不清楚这些差异是药物使用之前还是药物使用的结果。我们研究了大麻使用障碍(CUD)和一般物质使用和物质使用障碍责任(SU/SUD)的多基因风险评分(prs)对drug-naïve青少年脑形态的影响。基线数据来自1874名欧洲后裔参与者(9-11岁),分别包括222对MZ双胞胎、328对DZ双胞胎和387对非双胞胎兄弟姐妹,这些数据来自青少年大脑认知发展研究。我们拟合了多变量双胞胎模型来估计CUD、SU/SUD和脑区域特异性PRSs的假定影响。这些模型评估了它们对六种皮层下表型和两种皮层表型的影响。CUD和SU/SUD的PRS分别基于Johnson et al. (Lancet Psychiatry 7:1032, 2020)和Hatoum et al. (Nat Health 1:21 10-223, 2023)进行的GWAS创建。在分解每个感兴趣区域(ROI)的方差时,我们使用相应的ROI特定PRS。未用药受试者的脑形态测量与CUD PRS无关。每个ROI对应的PRS解释的方差在0.8到4.4%之间。SU/SUD PRS对皮层表面积和伏隔核体积的影响为0.2-0.4%,但总体效应较小。这项研究未能拒绝在基线吸毒青少年中物质使用的遗传风险与脑形态测量之间没有关联的原假设。在未接触毒品的青少年中,CUD的遗传风险与脑形态测量学无关,但与一般成瘾和物质使用风险(SU/SUD)有微弱关联,特别是在伏隔核体积和总皮质表面积方面。
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来源期刊
Behavior Genetics
Behavior Genetics 生物-行为科学
CiteScore
4.90
自引率
7.70%
发文量
30
审稿时长
6-12 weeks
期刊介绍: Behavior Genetics - the leading journal concerned with the genetic analysis of complex traits - is published in cooperation with the Behavior Genetics Association. This timely journal disseminates the most current original research on the inheritance and evolution of behavioral characteristics in man and other species. Contributions from eminent international researchers focus on both the application of various genetic perspectives to the study of behavioral characteristics and the influence of behavioral differences on the genetic structure of populations.
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