Behavioural Science Institute, Radboud University, Nijmegen, The Netherlands.
Amsterdam UMC, Amsterdam, The Netherlands.
Behav Genet. 2019 Jul;49(4):349-365. doi: 10.1007/s10519-019-09958-7. Epub 2019 May 20.
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.
研究测试单一遗传变异对物质使用的影响已经取得了一定的成功。本文综述了 39 项使用多基因措施测试与任何类型环境暴露（GxE）相互作用的研究，这些研究涉及酒精、烟草和大麻的使用。包括使用单倍型组合、候选基因风险等位基因总和评分和多基因评分（PS）的研究。总体研究质量为中等，单倍型和候选基因评分研究中的多基因方法评分较低。所研究的环境暴露、遗传因素和结果的异质性很大。大多数研究（N=30）报告了至少一个显著的 GxE 相互作用，但总体证据较弱。大多数研究（N=26）发现的结果与易感性差异和素质-应激框架一致。未来的研究应该更加注意方法学和统计学的严谨性，并专注于复制工作。在得出关于 GxE 在物质使用病因学中的重要性的明确结论之前，还需要做更多的工作。
