Integrating genome-wide association study with regulatory SNP annotation information identified candidate genes and pathways for schizophrenia.

BACKGROUND

Schizophrenia is a complex mental disorder. The genetic mechanism of schizophrenia remains elusive now.

METHODS

We conducted a large-scale integrative analysis of two genome-wide association studies of schizophrenia with functional annotation datasets of regulatory single-nucleotide polymorphism (rSNP). The significant SNPs identified by the two genome-wide association studies were first annotated to obtain schizophrenia associated rSNPs and their target genes and proteins, respectively. We then compared the integrative analysis results to identify the common rSNPs and their target regulatory genes and proteins, shared by the two genome-wide association studies of schizophrenia. Finally, DAVID tool was used to conduct gene ontology and pathway enrichment analysis of the identified targets genes and proteins.

RESULTS

We detected 53 schizophrenia-associated target genes for rSNP, such as FOS (P value = 2.18×10-20), ATXN1 (P value = 5.22×10-21) and HLA-DQA1 (P value = 1.98×10-10). Pathway enrichment analysis identified 24 pathways for transcription factors binding regions, chromatin interacting regions, long non-coding RNAs, topologically associated domains, circular RNAs and post-translational modifications, such as hsa05034:Alcoholism (P value = 2.57×10-7) and hsa04612:Antigen processing and presentation (P value = 6.82×10-8).

CONCLUSION

We detected multiple candidate genes, gene ontology terms and pathways for schizophrenia, supporting the functional importance of rSNPs, and providing novel clues for understanding the genetic architecture of schizophrenia.