The manifestation of genetic risk for psychiatric disorders in a general population sample of Swedish twin children

Psychiatric disorders are complex phenotypes. Molecular genetic studies have implicated numerous common risk variants that are, to a large extent, shared across different disorders. Recent studies suggest that genetic risk... [ view full abstract ]

Psychiatric disorders are complex phenotypes. Molecular genetic studies have implicated numerous common risk variants that are, to a large extent, shared across different disorders. Recent studies suggest that genetic risk variants for psychiatric disorders manifest as early childhood behavioural problems across a number of domains that are not always clearly associated with the psychiatric disorder (e.g. schizophrenia genetic risk is associated with social understanding difficulties and irritability at 7-9 years (Riglin et al. 2016)). We aimed to comprehensively test for association between genetic risk for 8 psychiatric phenotypes with a range of behavioural and psychiatric (e.g. neurodevelopmental and affective) phenotypes.

Genome-wide association study (GWAS) summary statistics for 8 psychiatric phenotypes were used to derive polygenic risk scores (PRS) in a Swedish population of twins (N=13,472 individuals) with data available at ages 9, 12, 15 and 18 years (Child & Adolescent Twin Study in Sweden). We tested for association between psychiatric disorder PRS with population traits (assessed using parent- and self-report questionnaires) and presence of psychiatric disorders (assessed through linkage with the Swedish National Patient Registry) in the sample.

After accounting for multiple testing, the results showed numerous significant associations across phenotypes. Schizophrenia PRS were associated with traits of attention-deficit/hyperactivity disorder (ADHD), autism, tics, obsessive-compulsive disorder (OCD), anxiety and depression. Bipolar disorder PRS were associated with autism traits. Depression PRS were associated with ADHD and OCD traits and diagnosed anxiety. OCD PRS were associated with anxiety traits and diagnosed autism and depression. ADHD PRS were associated with neurodevelopmental and affective (depressive and manic) problems. Autism PRS were associated with ADHD traits. Tic disorder and anxiety PRS showed no association with other phenotypes. This study provides further evidence for shared genetic risks across different clinical phenotypes. 

References:

Riglin, L. et al., 2016. Schizophrenia risk alleles and neurodevelopmental outcomes in childhood: a population-based cohort study. The Lancet Psychiatry.