Studies testing the effect of single genetic variants on substance use have had modest success. This paper reviewed 39 studies using polygenic measures to test interaction with any type of environmental exposure (G×E) in alcohol, tobacco, and cannabis use. Studies using haplotype combinations, sum scores of candidate-gene risk alleles, and polygenic scores (PS) were included. Overall study quality was moderate, with lower ratings for the polygenic methods in the haplotype and candidate-gene score studies. Heterogeneity in investigated environmental exposures, genetic factors, and outcomes was substantial. Most studies (N = 30) reported at least one significant G×E interaction, but overall evidence was weak. The majority (N = 26) found results in line with differential susceptibility and diathesis-stress frameworks. Future studies should pay more attention to methodological and statistical rigor, and focus on replication efforts. Additional work is needed before firm conclusions can be drawn about the importance of G×E in the etiology of substance use.

中文翻译：

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烟草、酒精和大麻使用中多基因基因-环境相互作用的系统评价。

测试单一基因变异对物质使用影响的研究取得了一定的成功。本文回顾了 39 项使用多基因措施来测试与酒精、烟草和大麻使用中任何类型的环境暴露 (G×E) 的相互作用的研究。包括使用单倍型组合、候选基因风险等位基因的总分和多基因评分 (PS) 的研究。总体研究质量中等，单倍型和候选基因评分研究中多基因方法的评分较低。调查的环境暴露、遗传因素和结果的异质性很大。大多数研究（N = 30）报告了至少一种显着的 G×E 相互作用，但总体证据较弱。大多数（N = 26）发现结果与差异易感性和素质压力框架一致。未来的研究应更加注重方法论和统计的严谨性，并注重重复性工作。在得出关于 G×E 在物质使用病因学中的重要性的确切结论之前，还需要进行额外的工作。