rs2297440

This functional study identifies rs3761124 as a causal variant on 20q13.33 that modulates glioma risk through enhancer activity and altered expression of multiple genes, particularly STMN3. Using luciferase assays, CRISPR-Cas9 editing, and eQTL analysis across 646 individuals from brain tissue and tumor cohorts, the authors demonstrate that rs3761124 has allele-specific effects on enhancer activity and consistently associates with STMN3 expression. Colocalization analysis (PP4=0.82) supports rs3761124 as the causal variant underlying the GWAS signal at this locus.

Age-stratified genome-wide association study of 4,512 glioblastoma cases and 10,582 controls identified age-specific genetic effects on disease susceptibility. SNPs at 7p11.2 (rs723527, rs11979158 near EGFR) showed increased association in older individuals (age 54+, OR=1.28-1.42), while a lower-grade glioma-associated SNP at 8q24.21 (rs55705857) was associated with younger diagnosis (age 18-53, OR=1.76, p=9.30×10−11). IDH1/2 mutations occurred in 15% of younger GBM cases versus 0.8-2.1% in older cases, suggesting many younger cases represent 'secondary GBM' with LGG-like features.