rs10979147 (RPS15AP27): Cutaneous Melanoma GWAS

Key takeaways

• rs10979147 is in the RPS15AP27 - RPL31P43 region, identified in a large genome-wide scan of cutaneous melanoma risk.
• In situ melanoma (confined to the skin surface) and invasive melanoma share roughly 96% of their genetic architecture, but variants still appear to tip the balance toward one form.
• Melanoma heritability (the share of disease risk explained by genetic factors) is modest: 6.7% for in situ and 4.9% for invasive forms, meaning most risk is non-genetic.
• A polygenic risk score combining effects across many variants predicted invasive vs. in situ melanoma with an odds ratio of 1.43 per standard deviation.

What the research says A 2024 genome-wide association study (GWAS) meta-analysis, which scans the full genome for statistical links between variants and a trait, examined germline genetic contributions to in situ and invasive cutaneous melanoma across four population-based cohorts (UK Biobank, FinnGen, QSkin Sun and Health Study, and Q-MEGA), identifying 6 genomic loci for in situ melanoma and 18 for invasive melanoma at genome-wide significance. The genetic correlation (a measure of shared genetic architecture) between the two subtypes was r = 0.96 (95% CI, 0.76-1.15), indicating largely overlapping but not fully identical risk factors. A polygenic risk score (PRS, a score combining small effects from many variants) built to distinguish invasive from in situ disease was significantly elevated in participants with invasive melanoma, with an odds ratio of 1.43 per 1-SD increase (95% CI, 1.16-1.77).

Reported associations

• Cutaneous melanoma (in situ): This locus was examined in a GWAS meta-analysis of four cohorts studying genetic risk for in situ cutaneous melanoma; the study identified 6 genome-wide significant loci for this subtype.
• Cutaneous melanoma (invasive): The same meta-analysis identified 18 genome-wide significant loci for invasive melanoma, with notably larger effects at IRF4, KLF4, and HULC for in situ disease and a larger effect at MC1R for invasive disease.

Evidence quality The meta-analysis incorporated data from four large population-based cohorts (UK Biobank, FinnGen, QSkin, and Q-MEGA) with records spanning 1987 to 2022. Heritability was 6.7% (95% CI, 4.1-9.3) for in situ melanoma and 4.9% (95% CI, 2.8-7.2) for invasive melanoma. The available study summary highlights named loci with differential subtype effects but does not provide variant-level effect sizes or confidence intervals specifically for rs10979147; detailed figures for this variant would require the full supplementary data. No conflicting findings were reported across the four contributing cohorts. Evidence for this specific variant should be considered preliminary pending variant-level replication.

Lifestyle considerations No lifestyle considerations on file for this variant.