Meta-analyses of RELN variants in neuropsychiatric disorders

Reelin is a critical extracellular matrix glycoprotein and implicated in neurodevelopment and psychiatric disorders in animal model studies. The genetic polymorphism of RELN has also been reported to be associated with several psychiatric disorders, but the results remain controversial. Here, we conducted meta-analyses of RELN gene SNPs and related neuropsychiatric disorders (schizophrenia, autistic spectrum disorders, attention-deficit hyperactivity disorder, Alzheimer's disease and bipolar disorders). A total of 12 SNPs (rs736707, rs362691, rs607755, rs2229864, rs7341475, rs262355, rs362719, rs11496125, g.-888G>C, rs2299356, rs528528, and rs4298437) in RELN gene were included into meta-analyses. Subgroup analyses based on ethnicity were performed. We found that RELN rs736707 was significantly related with psychiatric disorders (schizophrenia, autism spectrum disorders and attention-deficit hyperactivity disorder) in Asian group (C vs T, OR=1.26, 95% CI=1.13-1.41, P<0.01, FDR<0.01), and rs7341475 was only significantly associated with reduced risk of schizophrenia in Caucasian (A vs G, OR=0.88, 95% CI=0.82-0.95, P<0.01, FDR<0.01). No association of other SNPs and psychiatric disorders is found. These findings suggest a role of RELN SNPs in psychiatric diseases, and indicate that further researches in populations with different genetic background and studies with larger sample size are of great value.