Research Paper Volume 11, Issue 11 pp 3704—3715

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

Xiao Liang 1, *, , Sen Wang 1, *, , Li Liu 1, , Yanan Du 1, , Bolun Cheng 1, , Yan Wen 1, , Yan Zhao 1, , Miao Ding 1, , Shiqiang Cheng 1, , Mei Ma 1, , Lu Zhang 1, , Xin Qi 1, , Ping Li 1, , Xiong Guo 1, , Feng Zhang 1, ,

  • 1 Key Laboratory of Trace Elements and Endemic Diseases of National Health and Family Planning Commission, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, China
* Equal contribution

received: March 3, 2019 ; accepted: May 29, 2019 ; published: June 7, 2019 ;

https://doi.org/10.18632/aging.102008
How to Cite

Copyright: Liang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY 3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

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.

Abbreviations

GWAS: genome wide association studies; rSNP: regulatory SNP; TFBRs: transcription factor binding regions; CIRs: chromatin interactive regions; lncRNAs: long non-coding RNA regions; TADs: topologically associated domains; circRNAs: circular RNAs; PTMs: protein post-translational modifications; GO: gene ontology; SCZ: Schizophrenia.