Behavioural Science Institute, Radboud University Nijmegen, the Netherlands.
Behavioural Science Institute, Radboud University Nijmegen, the Netherlands; Department of Psychiatry, Amsterdam UMC, Amsterdam Neuroscience, University of Amsterdam, Amsterdam, the Netherlands.
Drug Alcohol Depend. 2020 Apr 1;209:107948. doi: 10.1016/j.drugalcdep.2020.107948. Epub 2020 Feb 28.
Tobacco, alcohol, and cannabis use are prevalent behaviors that pose considerable health risks. Genetic vulnerability and characteristics of the neighborhood of residence form important risk factors for substance use. Possibly, these factors do not act in isolation. This study tested the interaction between neighborhood characteristics and genetic risk (gene-environment interaction, GxE) and the association between these classes of risk factors (gene-environment correlation, rGE) in substance use.
Two polygenic scores (PGS) each (based on different discovery datasets) were created for smoking initiation, cigarettes per day, and glasses of alcohol per week based on summary statistics of different genome-wide association studies (GWAS). For cannabis initiation one PGS was created. These PGS were used to predict their respective phenotype in a large population-based sample from the Netherlands Twin Register (N = 6,567). Neighborhood characteristics as retrieved from governmental registration systems were factor analyzed and resulting measures of socioeconomic status (SES) and metropolitanism were used as predictors.
There were (small) main effects of neighborhood characteristics and PGS on substance use. One of the 14 tested GxE effects was significant, such that the PGS was more strongly associated with alcohol use in individuals with high SES. This was effect was only significant for one out of two PGS. There were weak indications of rGE, mainly with age and cohort covariates.
We conclude that both genetic and neighborhood-level factors are predictors for substance use. More research is needed to establish the robustness of the findings on the interplay between these factors.
吸烟、饮酒和使用大麻是普遍存在的行为，会对健康造成严重威胁。遗传易感性和居住环境特征是物质使用的重要风险因素。这些因素可能并非孤立存在。本研究检验了环境特征与遗传风险（基因-环境相互作用，GxE）之间的相互作用以及这些风险因素类别（基因-环境相关，rGE）之间的关联在物质使用中的作用。
根据不同全基因组关联研究（GWAS）的汇总统计数据，为吸烟起始、每天吸烟量和每周饮酒量创建了两个多基因评分（PGS），为大麻起始创建了一个 PGS。这些 PGS 用于预测荷兰双胞胎登记处（N = 6567）大型基于人群的样本中各自的表型。从政府登记系统中检索到的邻里特征进行因子分析，得出衡量社会经济地位（SES）和大都市主义的措施，并将其作为预测因子。
邻里特征和 PGS 对物质使用有（较小）的主要影响。测试的 14 个 GxE 效应中有一个具有统计学意义，即 PGS 与 SES 较高的个体的饮酒量相关性更强。这种效应仅在两个 PGS 中的一个中显著。存在 rGE 的微弱迹象，主要与年龄和队列协变量有关。
我们得出结论，遗传和邻里层面的因素都是物质使用的预测因素。需要进一步研究以确定这些因素之间相互作用的稳健性。
