Evaluation of shared genetic susceptibility loci between autoimmune diseases and schizophrenia based on genome-wide association studies

Abstract

Background: Epidemiological studies have documented higher than expected comorbidity (or, in some cases, inverse comorbidity) between schizophrenia and several autoimmune disorders. It remains unknown whether this comorbidity reflects shared genetic susceptibility loci.

Aims: The present study aimed to investigate whether verified genome wide significant variants of autoimmune disorders confer risk of schizophrenia, which could suggest a common genetic basis.

Methods: Seven hundred and fourteen genome wide significant risk variants of 25 autoimmune disorders were extracted from the NHGRI GWAS catalogue and examined for association to schizophrenia in the Psychiatric Genomics Consortium schizophrenia GWAS samples (36,989 cases and 113,075 controls).

Results: Two independent loci at 4q24 and 6p21.32–33 originally identified from GWAS of autoimmune diseases were found genome wide associated with schizophrenia (1.7 × 10⁻⁸≥p ≥ 4.0 × 10⁻²¹). While these observations confirm the existence of shared genetic susceptibility loci between schizophrenia and autoimmune diseases, the findings did not show a significant enrichment.

Conclusion: The findings do not support a genetic overlap in common SNPs between autoimmune diseases and schizophrenia that in part could explain the observed comorbidity from epidemiological studies.

Keywords:

• GWAS
• schizophrenia
• autoimmune diseases
• comorbidity

Acknowledgements

The authors are grateful to Stephan Ripke for assistance on the Psychiatric Genomics Consortium Schizophrenia GWAS samples. This study was financed through grants to Dr Werge from the Lundbeck Foundation (R34-A3243), the Danish National Advanced Technology Foundation (001-2009-2); the Danish Psychiatric Research Foundation and the European Union (LSHM-CT-2006-037761) and the Lundbeck Foundation, Denmark (R155-2014-1724).

Disclosure statement

Dr Werge has served as a lecturer for and consultant to H. Lundbeck A/S. The rest of the authors report no conflicts of interest.