Further evidence of VRK2 rs2312147 associated with schizophrenia

Abstract

Objectives: Previous genome-wide association studies (GWAS) have reported that rs2312147 near the VRK2 gene was significantly associated with schizophrenia in populations of European descent, but negative results have also been observed.

Methods: To perform a systematic meta-analysis, we collected statistical data of rs2312147 from both GWAS and individual replication samples in European and Asian populations, which finally included up to 30,867 schizophrenia patients and 59,863 healthy controls.

Results: The VRK2 rs2312147 was genome-wide significantly associated with schizophrenia in combined populations (P = 1.31 × 10⁻¹⁵, odds ratio, OR = 1.10) as well as in Europeans only (P = 2.35 × 10⁻¹², OR =1.09). In Asian samples, the SNP did not reach genome-wide level of statistical significance (P = 1.23 × 10 ^− 5, OR =1.19), which is likely due to the limited power of small sample size in this population (2,974 cases and 4,786 controls). However, the effect size of rs2312147 did not alter significantly between populations, and is also in agreement with the observed effect sizes of other genetic risk loci in large scale studies.

Conclusions: Our data provides further evidence for the genetic contributions of VRK2 rs2312147 to schizophrenia susceptibility especially in Europeans, while further replication analyses in Asian populations are still needed, and future studies, e.g., the underlying molecular mechanisms of genetic risk, are necessary.

Keywords:

• VRK2
• rs2312147
• schizophrenia
• GWAS
• meta-analysis

Acknowledgements

The authors are deeply grateful to the Psychiatric Genomics Consortium for sharing their GWAS statistics. The authors also thank Drs Anna Alkelai and Bernard Lerer (Biological Psychiatry Laboratory, Department of Psychiatry, Hadassah – Hebrew University Medical Centre, Jerusalem, Israel) for sharing the rs2312147 in their Jewish family-based samples. This work was supported by CAS Pioneer Hundred Talents Program.

Statement of interest

None to declare.