The specificity of genetic risk for psychiatric and substance use disorders: Its modification by age at onset, recurrence, and site of treatment

Individuals affected with a psychiatric disorder typically have elevated genetic risks for other mental disorders beyond the one from which they are currently suffering. From this observation it is possible to develop the concept of genetic specificity , defined in a cohort of affected individuals, as the proportion of the genetic risk for a set of psychiatric conditions due specifically to the disorder from which they are affected. To investigate this phenomenon, we studied all Swedish individuals born 1950 to 1995 with one of nine disorders ascertained from national registers: schizophrenia (SZ), bipolar disorder (BD), alcohol use disorder (AUD), ADHD, Autism spectrum disorder (ASD), PTSD, major depression (MD), anxiety disorder (AD) and drug use disorder (DUD). Genetic liabilities were calculated from family genetic risk scores. Specificity of genetic risk was defined as the proportion of genetic risk to all nine disorders due to genetic risk to the diagnosed disorder. The specificity of genetic risk varied from 29.5% for DUD to 73.1% for SZ. With increasing age at onset (AAO), genetic specificity decreased for BD and increased for PTSD. Higher levels of recurrence increased genetic specificity for all disorders with the largest effects on BD and ADHD. Genetic specificity was highest with hospitalized cases for BD while for PTSD, AD and MD, specificity was highest in primary care cases. Common psychiatric disorders differ widely in their degrees of genetic specificity. The genetic specificity for many disorders can vary substantially as a function of AAO, level of recurrence, and site of treatment.