TY - JOUR
T1 - Genetic liability for schizophrenia predicts risk of immune disorders
AU - Stringer, Sven
AU - Kahn, René S.
AU - de Witte, Lot D.
AU - Ophoff, Roel A.
AU - Derks, Eske M.
N1 - Publisher Copyright:
© 2014 Elsevier B.V.
PY - 2014/11/1
Y1 - 2014/11/1
N2 - 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 schizophrenia.
AB - 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 schizophrenia.
KW - Genetic overlap
KW - Genome-wide association study
KW - Human leukocyte antigen system
KW - Immune dysregulation
KW - Major histocompatibility complex
KW - Polygenic risk score
UR - http://www.scopus.com/inward/record.url?scp=84922450900&partnerID=8YFLogxK
U2 - 10.1016/j.schres.2014.09.004
DO - 10.1016/j.schres.2014.09.004
M3 - Article
C2 - 25266548
AN - SCOPUS:84922450900
SN - 0920-9964
VL - 159
SP - 347
EP - 352
JO - Schizophrenia Research
JF - Schizophrenia Research
IS - 2-3
ER -