rs10896090

This functional genomic study identified 16 transcription factor binding-disrupting SNPs across reported bipolar disorder (BD) GWAS loci and elucidated their regulatory mechanisms. Using eQTL analysis, CRISPR/Cas9 editing, and functional assays, the authors demonstrated that rs10896081 disrupts PBX3 binding to regulate PACS1 and YIF1A expression, and that rs3862386 similarly regulates PACS1 expression. PACS1 overexpression affected dendritic spine density in neurons, suggesting a mechanistic link between these functional SNPs and BD risk through regulation of genes involved in synaptic function.

A case-control association study of 1,237 Pakistani subjects (479 with major depression, 222 with bipolar disorder, 146 with schizophrenia, 390 controls) examined 11 dopaminergic system gene variants. Significant risk associations were found for rs1006737 and rs2238056 (CACNA1c) with bipolar disorder (OR=1.14-1.15), while rs10033951 (DRD5), rs2388334 (POU3F2), and the DRD4 120bp VNTR showed protective effects across disorders (OR=0.81-0.86).