rs554219

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 two-phase association study of 1,414 SNPs in steroid hormone and IGF-1 metabolism genes investigated breast cancer in situ (BCIS) risk in 1,062 cases and 10,126 controls from the Breast and Prostate Cancer Cohort Consortium. INSR-rs10500204 showed significant association with increased BCIS risk (OR=1.96 for homozygous major allele, p=1.68×10⁻⁵), being more strongly associated with BCIS than invasive disease. Two other SNPs (ACVR2A-rs2382112 and MAST2-rs12124649) showed nominally significant but less robust associations.