We know little about how genetic risk factors for two disorders jointly act and interact in predisposing to illness. Therefore, in the Swedish population, born 1970–1990 (n = 2,116,082) and followed through 2015, we examine, using additive Cox models, the impact of the family genetic risk scores (FGRS) for alcohol use disorder (AUD) and major depression (MD), their interaction with each other and with the relevant comorbid disorder on risk for AUD and MD. FGRS scores are constructed using rates of illness in first-fourth degree relatives. FGRS for AUD and MD interacted in predicting of both disorders and one FRGS (e.g., for AUD) interacted with the phenotype of MD to predict that disorder (e.g., AUD). These FGRS interactions were not substantially attenuated by adding interactions with the disorders. These results replicated across sexes. In predicting risk for a given disorder, we rarely consider genetic liabilities for other disorders. But such effects were here significant and interactive. Furthermore, the primary disorder genetic risk interacts with comorbid disorders. The pathways to risk for disorders from their and other disorders' genetic liability may be more complex than commonly considered.

中文翻译：

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酒精使用障碍和重度抑郁症的家庭遗传风险评分对这两种疾病风险的作用和相互作用


我们对两种疾病的遗传风险因素如何共同作用和相互作用以诱发疾病知之甚少。因此，在 1970-1990 年出生（ n = 2,116,082）并持续到 2015 年的瑞典人口中，我们使用附加 Cox 模型检查了家庭遗传风险评分 (FGRS) 对酒精使用障碍 (AUD) 和重度抑郁症的影响(MD)，它们之间的相互作用以及它们与相关共病疾病对 AUD 和 MD 风险的相互作用。 FGRS 评分是根据一级亲属的患病率构建的。 AUD 和 MD 的 FGRS 在预测两种疾病时相互作用，并且一种 FRGS（例如，AUD）与 MD 的表型相互作用，以预测该疾病（例如，AUD）。这些 FGRS 相互作用并未因增加与疾病的相互作用而显着减弱。这些结果在不同性别之间得到了复制。在预测特定疾病的风险时，我们很少考虑其他疾病的遗传倾向。但这种影响在这里是显着且互动的。此外，原发性疾病遗传风险与合并症相互作用。其疾病和其他疾病的遗传倾向导致疾病风险的途径可能比通常认为的更为复杂。