rs2274567

This is the first genome-wide association study (GWAS) of hippocampal sclerosis of aging (HS-Aging), a common neuropathology in elderly individuals. The study analyzed 363 HS-Aging cases and 2,303 controls from multiple autopsy cohorts and identified that rs704178:G in the ABCC9 gene (ATP-binding cassette, sub-family C member 9, also known as sulfonylurea receptor 2) is associated with HS-Aging pathology with genome-wide significance (p = 1.4 × 10⁻⁹, OR = 2.13 in recessive mode). The authors also confirmed previously identified associations with rs5848 (GRN, OR = 1.16) and rs1990622 (near TMEM106B, OR = 1.22). Additionally, sulfonylurea drug exposure in elderly subjects (n = 624, age ≥85 at death) was associated with increased HS-Aging risk (p = 0.03), identifying a potentially targetable dementia risk factor.

Genome-wide association study of hippocampal sclerosis of aging (HS-Aging) pathology in 363 cases and 2,303 neuropathologically confirmed controls found that rs704178 in the ABCC9 gene (sulfonylurea receptor 2) was significantly associated with HS-Aging (p = 1.4 × 10⁻⁹, OR = 2.13 recessive). Sulfonylurea drug exposure was also associated with HS-Aging risk (p = 0.03) in elderly individuals age 85+. Previously reported SNPs rs5848 (GRN) and rs1990622 (TMEM106B) showed trends toward association with similar effect sizes.

This whole-exome sequencing study identified maternal coding variants in complement and coagulation pathway genes contributing to spontaneous idiopathic preterm birth (PTB). Variants in the complement receptor 1 gene (CR1) showed significant association with PTB in a Finnish case-control cohort (237 cases, 328 controls), with the strongest association at rs6691117 (p=6.91e-5, OR=1.71). Additional intronic CR1 variants rs10429953 (OR=1.93) and rs10429943 (OR=1.84) also showed significant associations, suggesting the complement/coagulation cascade pathway plays an important role in PTB pathophysiology.