Analysis of common genetic variants identifies RELN as a risk gene for schizophrenia in Chinese population

Abstract

Objectives. Several lines of evidence have shown that both RELN mRNA and protein are possibly down-regulated in the brain of schizophrenia patients. Recent association studies in European populations suggested RELN as a risk gene for schizophrenia. In this study, we test if RELN contributes to the risk of schizophrenia in Chinese population. Methods. We conducted case-control association analysis of 19 representative single nucleotide polymorphisms (SNPs) spanning the entire region of RELN in two independent Han Chinese samples from southwestern China (the Kunming sample and the Yuxi sample). Results. We identified six SNPs significantly associated with schizophrenia in the Kunming sample and four of them remained significant in the combined samples (the P values range from 0.006 to 4.0 × 10⁻⁵). Haplotype analysis also suggested significant associations for the haplotypes incorporating the six significant SNPs (global P < 1.0 × 10⁻⁵). Additionally, we also observed several other haplotypes (defined by a different set of SNPs) significantly associated with schizophrenia in the Kunming sample. However, the reported association of rs7341475 in Ashkenazi Jews was not significant in Han Chinese. Conclusions: Our findings demonstrate that RELN is a susceptibility gene for schizophrenia in Chinese population, and it is likely a common risk gene for schizophrenia in major populations worldwide.

Key words::

• RELN
• single nucleotide polymorphism
• haplotype
• schizophrenia
• Chinese population

Acknowledgements

This work was supported by grants from the National 973 project of China (grant numbers, 2011CBA00401 and 2007CB947701), the National Natural Science Foundation of China (grant numbers, 30871343 and 31071101), and the Natural Science Foundation of Yunnan Province of China (grant numbers, 2007C100M and 2009CD107). We are grateful to all the voluntary donors of DNA samples in this study. We thank Hui Zhang and Yanjiao Li for their technical assistance in this study.

Statement of Interest

The authors have no conflicts of interest to declare.