Impact of comorbidity on family genetic risk profiles for psychiatric and substance use disorders: a descriptive analysis

• Published in: Psychological medicine Vol. 53; no. 6; pp. 2389 - 2398
• Main Authors: Kendler, Kenneth S., Ohlsson, Henrik, Sundquist, Jan, Sundquist, Kristina
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.04.2023
• Subjects: Autism; Clinical Medicine; Cohabitation; Comorbidity; Consortia; Developmental disabilities; Developmental disorders; Drug use; Ethics; Family; Genetic susceptibility; Health risk assessment; Humans; Internalization; Klinisk medicin; Males; Medical and Health Sciences; Medicin och hälsovetenskap; Mental disorders; Original Article; Psychiatry; Psychosis; Psykiatri; Registries; Substance use; Substance use disorder; Substance-Related Disorders - epidemiology; Substance-Related Disorders - genetics; Twins; Sweden; family genetic risk scores; psychiatric and substance use disorders; Comorbidity; mechanisms
• ISSN: 0033-2917; 1469-8978; 1469-8978
• DOI: 10.1017/S0033291721004268

- Comorbidity between psychiatric disorders is extensive but, from a genetic perspective, still poorly understood. Modern molecular genetic approaches to this problem are limited by a reliance on case-control designs. - In 5 828 760 individuals born in Sweden from 1932-1995 with a mean (s.d.) age at follow-up of 54.4 (18.1), we examined family genetic risk score (FGRS) profiles including internalizing, psychotic, substance use and developmental disorders in 10 pairs of psychiatric and substance use disorders diagnosed from population registries. We examined these profiles in three groups of patients: disorder A only, disorder B only and comorbid cases with both disorders. - The most common pattern of findings, seen in five pairings, was simple and quantitative. Comorbid cases had higher FGRS than both non-comorbid cases for all (or nearly all) disorders. However, the pattern was more complex in the remaining five pairings and included qualitative changes where the comorbid cases showed no increases in FGRS for certain disorders and in a few cases significant decreases. Several comparisons showed an asymmetric pattern of findings with increases, in comorbidity compared to single disorder cases, of the FGRS for only one of the two disorders. - The examination of FGRS profiles in general population samples where all disorders are assessed in all subjects provides a fruitful line of inquiry to understand the origins of psychiatric comorbidity. Further work will be needed, with an expansion of analytic approaches, to gain deeper insights into the complex mechanisms likely involved.