The cannabinoid receptor-1 gene interacts with stressful life events to increase the risk for problematic alcohol use.

For instance, there was a tendency towards increased neuroticism in individuals who had experienced child SLEs, and this tendency was strongest among C-allele homozygotes, but the interaction terms in the regression model did not reach statistical significance (Fig.

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However, there was a clear trend for interaction between rs2023239’s risk allele (C) and stressful life events (SLEs) in both childhood and adulthood, which predicted problematic alcohol use.

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Previous GWAS have found nominally significant associations between the C-allele and addiction-related outcomes, including the number of unsuccessful stop-smoking attempts and the frequency of feeling guilt or remorse after drinking alcohol in the last year 96 .

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