rs3130297

A candidate gene association study of HLA-DRB1 tagging SNPs in schizophrenia among 332 British cases (219 male, 113 female; mean age 32-36 years) and 155 controls (mean age 40-42 years) recruited through family-based (132 trios, 92 duos) and case-control designs. The DRB1*1303 allele showed marginal protective association (OR=0.42, 95% CI 0.27-0.66, χ²=4.138, P=0.042), and rs424232 showed significant protective association with schizophrenia (OR=0.69, 95% CI 0.54-0.88, χ²=9.404, P=0.002). The authors failed to confirm association of candidate DRB1 risk alleles but noted the association signal may extend beyond the HLA locus toward the NOTCH4 gene.

This review comprehensively summarizes the latest genetic studies on schizophrenia, including family studies (heritability ~80%), genome-wide association studies, epigenetic mechanisms, candidate gene investigations, and next-generation sequencing findings. Key GWAS findings identified 108 schizophrenia-associated loci including variants in MIR137 (rs1625579), TCF4 (rs12966547), CSMD1 (rs10503253), CACNA1C (rs4765905), ANK3 (rs10761482), and MHC region variants, with evidence for polygenetic inheritance involving both common SNPs and rare copy number variations.