The patterns of family genetic risk scores for eleven major psychiatric and substance use disorders in a Swedish national sample

Abstract

To clarify the structure of genetic risks for 11 major psychiatric disorders, we calculated, from morbidity risks for disorders in 1st-5th degree relatives controlling for cohabitation effects, in the Swedish population born between 1932 and 1995 (n = 5,830,014), the family genetic risk scores (FGRS) for major depression (MD), anxiety disorders (AD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), bulimia (BUL), anorexia nervosa (AN), alcohol use disorder (AUD), drug use disorder (DUD), ADHD, and autism-spectrum disorder (ASD). For all affected individuals, we calculated their mean standardized FGRS for each disorder. The patterns of FGRS were quite similar for MD and AD, and for AUD and DUD, but substantially less similar for BUL and AN, BD and SZ, and ADHD and ASD. While OCD had high levels of FGRS for MD and AD, the overall FGRS profile differed considerably from MD and AD. ADHD FGRS scores were substantially elevated in AUD and DUD. FGRS scores for BD, OCD, AN, ASD, ADHD, and especially SZ were relatively disorder-specific while genetic risk for MD and AD had more generalized effects. The levels of FGRS for BMI, coronary artery disease, and educational attainment across our disorders replicated prior associations found using molecular genetic methods. All diagnostic categories examined had elevated FGRS for many disorders producing, for each condition, an informative FGRS profile. Using a novel method which approximates, from pedigree data, aggregate genetic risk, we have replicated and extended prior insights into the structure of genetic risk factors for key psychiatric illnesses.

Fig. 1. The mean Genetic Risk Score for 11 disorders in individuals diagnosed with those 11 disorders grouped by Disorder.

The y-axis is the mean z-score for the genetic risk scores. The disorders are: major depression (MD), anxiety disorders (AD), obsessive-compulsive disorder (OCD), bipolar disorder (BD), schizophrenia (SZ), bulimia (BUL), anorexia nervosa (AN), alcohol use disorder (AUD), drug use disorder (DUD), ADHD, and autism-spectrum disorder (ASD). For clarity, we provide different color codes for the disorders divided into five categories of internalizing disorders (MD, AD, and OCD), psychotic disorders (BD and SZ), eating disorders (BUL and AN), substance use disorders (AUD and DUD), and neurodevelopmental disorders (ADHD and ASD).

Fig. 2. The mean genetic risk score for 11 disorders in individuals diagnosed with those 11 disorders grouped by genetic risk score.

In this figure, the individual genetic risk scores are grouped by genetic risk score, from highest to lowest score, not by disorder as in Fig. 1. The y-axis is the mean z-score for the genetic risk scores. For initials of the disorders, see Fig. 1 legend.

Fig. 3. Validation of the FGRS Scores.

The mean genetic risk score for body mass index (BMI), coronary artery disease (CAD), and years of education (YOE) in 11 disorders ascertained from the general Swedish population. The y-axis is the mean z-score for the genetic risk scores. The disorders are ranked from highest to lowest score.