# The moderation of genetic risk for ten major psychiatric and substance use disorders by the genetic aptitude for educational attainment

## TL;DR

This study shows how genetic factors related to educational success can influence the risk of various mental health disorders, with different effects depending on the type of disorder.

## Contribution

The study reveals how genetic aptitude for education interacts with disorder-specific genetic risks in psychiatric and substance use disorders.

## Key findings

- GAEA is strongly linked to reduced risk for externalizing and internalizing disorders.
- GAEA interacts with genetic risk factors, altering the risk slope for different disorders.
- The effects of GAEA on disorder risk vary in magnitude, direction, and mediation across disorders.

## Abstract

We seek to clarify the impact of the Genetic Aptitude for Educational Attainment (GAEA) on risk for 10 psychiatric disorders divided into 4 groups: Internalizing, Externalizing, Eating/Compulsive and Psychotic. Educational attainment and psychiatric and substance use disorder information were obtained from national Swedish registries. GAEA and disorder-specific family genetic risk score (FGRS) were calculated from extended pedigrees. In males, information on IQ and resilience was obtained from the Swedish conscript registry. Affected individuals were born in Sweden from 1973–1995 to Swedish born parents. Controlling for disorder specific FGRS, GAEA were negatively and substantially associated with risk for externalizing and internalizing disorders, minimally associated with psychotic disorder risk and positively and modestly associated with risk for eating/compulsive disorders. While the majority of GAEA effect on risk for externalizing disorders was mediated through impact on IQ, for internalizing disorders, mediation was largely through resilience. For externalizing and internalizing disorders, interactions between GAEA and disorder specific FGRS were robust and negative – the slope of disorder risk with increasing genetic liability was steepest in those with low GAEA. For eating disorders, interactions were modest and positive –the slope of risk with increasing genetic liability being steepest in individuals with high GAEA. We found that the impact of GAEA on risk for psychiatric and substance can be substantial and varies widely across disorders in magnitude, direction, and mediation. GAEA also often interacts, sometimes robustly, with disorder specific genetic risk factors. Comprehensive risk models for psychiatric disorders should consider the inclusion of GAEA.