SNX29, a new susceptibility gene shared with major mental disorders in Han Chinese population

Abstract

Objectives

Environmental and genetic factors play important roles in the development of schizophrenia (SCZ), bipolar disorder (BPD) or major depressive disorder (MDD). Some risk loci are identified with shared genetic effects on major psychiatric disorders. To investigate whether SNX29 gene played a significant role in these psychiatric disorders in the Han Chinese population.

Methods

We focussed on 11 single-nucleotide polymorphisms (SNPs) harbouring SNX29 gene and carried out case–control studies in patients with SCZ (n = 1248), BPD (n = 1344), or MDD (n = 1056), and 1248 healthy controls (HC) recruited from the Han Chinese population. We constructed weighted gene co-expression network analysis (WGCNA) and extracted significant modules by R package.

Results

We found that rs3743592 was significantly associated with MDD and rs6498263 with BPD in both allele and genotype distributions. Before correction, rs3743592 showed allelic and genotypic significance with SCZ, rs6498263 showed allelic significance with SCZ. WGCNA identified top 10 modules of co-expressed genes. Gene Ontology (GO) and pathway analysis were used to examine the functions of SNX29, which revealed that SNX29 was involved in the regulation of a number of biological processes, such as TGF-beta, ErbB, and Wnt signalling pathway, etc.

Conclusions

Our results supported common risk factors in SNX29 might share among these three mental disorders in the Han Chinese population.

Keywords:

• SNX29
• bipolar disorder
• major depressive disorder
• schizophrenia
• cross-disease

Acknowledgements

The authors are deeply grateful to all the patients and HC participating in this study as well as to the psychiatrists for their help in the recruitment and diagnosis of SCZ, BPD and MDD patients. The authors also thank Mr. Bo Zhang and the NovelBio Co., Ltd. for technical support.

Disclosure statement

The authors declare no conflict of interest.

Additional information

Funding

This work was supported by the National Key R&D Program of China [2016YFC1306900, 2017YFC0908105, 2019YFA0905400], the Natural Science Foundation of China [U1804284, 82071500, 81871055, 81871051], the 973 Program [2015CB559100], the Program of Shanghai Subject Chief Scientist [15XD1502200], the National Program for Support of Top-Notch Young Professionals, Shanghai Key Laboratory of Psychotic Disorders [13dz2260500], Shanghai Municipal Science and Technology Major Project [2017SHZDZX01, 2018SHZDZX05], the National Program for Support of Top-Notch Young Professionals to Y.S., R.S. is part-funded by the National Institute for Health Research (NIHR) Biomedical Research Centre at the South London and Maudsley NHS Foundation Trust and King’s College London, Shanghai Hospital Development Center [SHDC12017X12, SHDC12016115], Shanghai Youth Top-notch Talent Support Program to J.C., Scientific Research and Development Fund of Shanghai Jiao Tong University [19X150010012], Shanghai Municipal Education Commission-Gaofeng Clinical Medicine Grant Support, Innovative research team of high-level local universities in Shanghai and Shanghai Clinical Research Center for Mental Health [19MC1911100].