BACKGROUND:Schizophrenia patients and their parents have an
increased risk of immune disorders compared to population controls and
their parents. This may be explained by genetic overlap in the
pathogenesis of both types of disorders. The purpose of this study was
to investigate the genetic overlap between schizophrenia and three
immune disorders and to compare with the overlap between schizophrenia
and two disorders not primarily characterized by immune dysregulation:
bipolar disorder and type 2 diabetes.
METHODS:We performed a polygenic risk score analysis using results from the
schizophrenia Psychiatric GWAS consortium (PGC) (8922 cases and 9528
controls) and five Wellcome Trust Case Control Consortium (WTCCC) case
samples as target cases: bipolar disorder (n=1998), type 1 diabetes
(n=2000), Crohn's diseases (n=2005), rheumatoid arthritis (n=1999), and
type 2 diabetes (n=1999). The WTCCC British Birth Cohort and National
Blood Service samples (n=3004) were used as target controls.
Additionally, we tested whether schizophrenia polygenic risk scores
significantly differed between patients with immune disorder, bipolar
disorder, and type 2 diabetes respectively.
RESULTS:Polygenic risk scores for schizophrenia significantly predicted disease status in
all three immune disorder samples (Nagelkerke-R2 1.1%-1.3%;
p<0.05). The polygenic risk of schizophrenia in patients with immune
disorders was significantly lower than in patients with bipolar disorder
(Nagelkerke-R2 6.0%; p<0.05), but higher than in type 2 diabetes patients (Nagelkerke-R2 0.5%; p<0.05).
CONCLUSIONS:Our results suggest that genetic factors are shared between schizophrenia
and immune disorders. This contributes to an accumulating body of
evidence that immune processes may play a role in the etiology of