Genetics

Glaucoma polygenic risk score stratifies lifetime risk and need for escalated care

In 402,739 FinnGen participants, the best glaucoma PRS showed HR 3.32 for glaucoma comparing ≥90th versus 20–80th percentiles. Lifetime glaucoma risk by age 85 ranged from 2.5% (<1st percentile) to 45.3% (≥99th percentile). Highest PRS decile had greater 20-year cumulative rates of medication escalation (60.6% vs 38.4%), laser (39.8% vs 22.9%), and surgery (15.8% vs 9.5%). PRS effect was largely independent of family history and provided finer risk stratification by midlife. This is observational biobank evidence; prospective studies are needed before routine clinical deployment. 1

FinnGen biobank reveals enriched rare variants and genotype-phenotype links for neurodegeneration

FinnGen combines half a million genotyped participants with nationwide registries, enriching rare-variant discovery in a genetically isolated population. Analyses have identified thousands of genotype-phenotype associations, including novel protein‑altering variants relevant to AD and iNPH. The cohort overrepresents older and hospital-derived samples, increasing power for brain-disorder studies but limiting generalizability. Integration with recall, biomarker, and clinical data is highlighted as the pathway to accelerate translational application. 2

Mean polygenic risk for ASD and ADHD decreased in more recent diagnosis cohorts

In Danish iPSYCH data (17,071 ASD; 20,111 ADHD cases), later year of diagnosis associated with lower mean polygenic scores for ASD and ADHD. Effect sizes were modest (eg, β per 10-year increase ≈ -0.06 to -0.07 SDs across disorders) but consistent across multiple psychiatric PGSs. Findings align with diagnostic expansion or altered ascertainment as drivers of rising ASD/ADHD incidence rather than increased genetic burden. These observational trends do not identify specific environmental causes and should inform epidemiologic interpretation, not individual risk prediction. 3