Further evidence for the association between LRP8 and schizophrenia.

Previous studies (including genome-wide association study (GWAS) and candidate gene studies) have revealed the important roles of genetic risk factors in schizophrenia, and RELN has been identified as a risk gene for this illness. We recently found that the low-density lipoprotein receptor-related protein 8 (LRP8), a receptor of Reelin (the protein encoded by RELN), was significantly associated with schizophrenia and bipolar disorder in European populations. To further enhance our understanding of its role in the risk of psychiatric illnesses, we conducted meta-analyses of a higher density of single nucleotide polymorphisms (SNPs, N=173) in LRP8 to understand their associations with schizophrenia in much larger samples (39,400 cases and 50,357 controls) from populations of European, Chinese and African American ancestries. The significant risk SNPs then underwent further analyses to understand their correlations with bipolar disorder and anxiety disorders, as well as LRP8 expression. We observed that rs5177 in the 3' untranslated region (3'UTR) of LRP8 was associated with schizophrenia and other psychiatric disorders, and rs5177 was also associated with LRP8 mRNA expression. These data further support LRP8 as a schizophrenia susceptibility gene, and suggest that this variant is likely a risk locus in general populations.