Department of Psychiatry, Robert Wood Johnson Medical School, Rutgers University (Salvatore); Center for Primary Health Care Research, Lund University, Malmö, Sweden (Ohlsson, Jan Sundquist, Kristina Sundquist); Virginia Institute for Psychiatric and Behavioral Genetics, Department of Psychiatry, and Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond (Kendler).
Am J Psychiatry. 2024 Sep 1;181(9):824-833. doi: 10.1176/appi.ajp.20230358. Epub 2024 Aug 7.
There is growing interest in how peers' genotypes may influence health (i.e., peer social genetic effects). The authors sought to clarify the nature of peer social genetic effects on risk for drug use disorder, alcohol use disorder (AUD), major depression, and anxiety disorder.
Cox models were used with data from a population-based Swedish cohort (N=655,327). Outcomes were drug use disorder, AUD, major depression, and anxiety disorder registrations between ages 17 and 30 from medical, criminal, and pharmacy registries. The authors indexed peer social genetic effects with peers' family genetic risk scores (FGRSs) for the same disorders, which are personalized measures of genetic risk inferred from diagnoses in first- to fifth-degree relatives.
Across disorders, peer FGRSs predicted increased risks of proband registration (hazard ratio range, 1.01-1.59), with stronger effects for drug use disorder and AUD than for major depression and anxiety disorder. Peer social genetic effects were stronger for school classmates than for geographically proximal peers, and for peers from upper secondary school (ages 16-19) versus peers from lower secondary school (ages 7-16). Peer social genetic effects remained significant following statistical control for sociodemographic confounders, whether peers were affected, and peers' FGRS for educational attainment. Peer social genetic effects were more pronounced for probands at higher genetic risk.
The genetic makeup of adolescents' peers has long-reaching consequences on risks for drug use disorder, AUD, major depression, and anxiety disorder. Individuals at high genetic risk are more sensitive to social genetic effects. Alternative hypotheses such as sociodemographic stratification, exposure to affected peers, and genetic predispositions for educational attainment did not explain the risk associated with peer social genetic effects for substance use and psychiatric disorders.
人们越来越关注同伴的基因型如何影响健康（即同伴社交遗传效应）。作者试图阐明同伴社交遗传效应对药物使用障碍、酒精使用障碍（AUD）、重度抑郁症和焦虑症风险的影响。
作者使用来自基于人群的瑞典队列（N=655,327）的数据，采用 Cox 模型。结局为 17 至 30 岁时，从医疗、刑事和药房登记处登记的药物使用障碍、AUD、重度抑郁症和焦虑症。作者用同伴的家族遗传风险评分（FGRS）来索引同伴社交遗传效应，这些评分是根据一级至五级亲属的诊断推断出的个性化遗传风险指标。
在各种疾病中，同伴 FGRS 预测了患者登记的风险增加（危险比范围为 1.01-1.59），药物使用障碍和 AUD 的影响大于重度抑郁症和焦虑症。与地理上相近的同伴相比，与同学的同伴社交遗传效应更强，与来自中学（16-19 岁）的同伴相比，与来自中学（7-16 岁）的同伴的社交遗传效应更强。在对社会人口统计学混杂因素、同伴是否受影响以及同伴的教育程度 FGRS 进行统计控制后，同伴社交遗传效应仍然显著。对于遗传风险较高的患者，同伴社交遗传效应更为明显。
青少年同伴的基因构成对药物使用障碍、AUD、重度抑郁症和焦虑症的风险具有深远的影响。遗传风险较高的个体对社交遗传效应更为敏感。替代假设，如社会人口统计学分层、受影响同伴的暴露以及教育程度的遗传倾向，都不能解释与物质使用和精神障碍相关的同伴社交遗传效应所带来的风险。
