Background

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.

Methods

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.

Results

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.

Conclusion

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.

中文翻译：

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物质使用：多基因风险与邻里环境之间的相互作用

背景

烟草，酒精和大麻的使用是普遍的行为，构成相当大的健康风险。遗传易感性和居住区的特征是物质使用的重要危险因素。这些因素可能并非孤立地起作用。这项研究测试了邻里特征和遗传风险之间的相互作用（基因-环境相互作用，GxE）以及物质使用中这些类别的危险因素之间的关联（基因-环境相关性，rGE）。

方法

根据不同的全基因组关联研究（GWAS）的摘要统计，分别创建了两个多基因评分（PGS）（基于不同的发现数据集）用于吸烟，每天吸烟和每周饮酒。为了启动大麻，创建了一个PGS。这些PGS被用于预测来自荷兰双胞胎登记册（N = 6,567）的大量人群样本中的各自表型。对从政府注册系统中检索到的邻里特征进行了因子分析，并将由此得出的社会经济地位（SES）和大都市主义测度用作预测因子。

结果

邻里特征和PGS对物质使用有（小的）主要影响。经测试的14种GxE效果之一是显着的，因此PGS与高SES个体的饮酒关联更强。仅对于两个PGS中的一个，此效果才有意义。rGE的迹象较弱，主要与年龄和队列协变量有关。

结论

我们得出结论，遗传因素和邻里水平因素都是物质使用的预测因素。需要更多的研究来确定这些因素之间相互作用的结果的稳健性。