Genetics

Genetic testing completion and diagnostic yield vary by race, age, sex, and phenotype in hereditary eye disorders.

In 1466 patients seen at a tertiary genetic eye clinic, 74% completed genetic testing and 62% achieved a likely molecular diagnosis. Younger age, earlier symptom onset, longer follow-up, worse visual acuity, male sex, and syndromic or X-linked phenotypes increased diagnostic yield. Black and Other race participants had lower odds of testing completion (Black OR 0.40) and molecular diagnosis (Black OR 0.37). Racial disparities persisted despite similar or shorter time to testing, suggesting barriers beyond care delays. 1

Epilepsy polygenic risk scores show variable predictive value across Taiwanese cohorts and ages.

PRS for genetic generalized epilepsy (GGE) showed the strongest effect in the clinically ascertained Epi25-TWN cohort (per-unit OR 1.65, R2 3.2%). In population cohorts (TWB-NHIRD, TPMI) GGE PRS effects were smaller (ORs ~1.09–1.13; R2 ≤0.22%), and focal epilepsy PRS effects were modest. Top 5% GGE PRS conferred >4-fold risk in Epi25-TWN but <1.5-fold in population cohorts, and restricting to earlier onset strengthened signals. Authors emphasize cohort design and phenotyping accuracy substantially influence PRS performance and clinical interpretation. 2

Mendelian randomization synthesis prioritizes modifiable exposures for vascular dementia prevention.

A structured synthesis of 74 MR studies yielded 1002 estimates and prioritized cerebrovascular events, diabetes/hyperglycaemia, inflammatory and iron-handling markers, and some neuropsychiatric traits. Traditional risk factors such as specific lipid fractions and blood pressure showed inconsistent MR evidence across estimators. The framework ranks signals for replication and trial targeting rather than establishing definitive clinical causality. Findings guide selection of exposures for prevention trials and mechanistic validation in vascular dementia. 3