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PubMed2026

Genome-wide discovery reveals 30 loci for choroidal thickness and uncovers potential causal links with angle-closure glaucoma.

The choroid is critical for maintaining vision and implicated in several ocular diseases, being the sole source of nutrients and waste removal for the outer retina. Genetic discovery can help elucidate the pathways through which choroidal features influence disease risk. Our meta-analysis of genome-wide association studies (n= 78,682 participants) identified 30 genomic regions, including 20 novel loci, associated with choroidal thickness. Findings suggest inflammatory and vascular processes drive choroidal thickness, with overlapping mechanisms shared with refractive error. Genome-wide independently significant SNPs accounted for 18.7% of the genetic variance in choroidal thickness. Mendelian randomisation analyses showed a causal effect of age-related macular degeneration on choroidal thickness, and suggest a bidirectional causal effect between choroidal thickness and primary angle-closure glaucoma. These findings provide insight into the shared genetic architecture and biological pathways linking choroidal thickness and related diseases.

Canadian Longitudinal Study on Aging↗

PubMed2025

Polygenic Risk Scores for Preeclampsia Prediction Beyond Gold-Standard Clinical Models in Multiethnic Populations.

BACKGROUND: Preeclampsia is a major cause of maternal and fetal mortality and morbidity. Early risk stratification enables timely preventative therapy in high-risk women. Polygenic risk scores (PGS) improve prediction in complex diseases, but their added value for preeclampsia remains unclear, particularly in comparison to gold-standard first-trimester prediction models and across non-European ancestries. METHODS: We evaluated the performance of both a preeclampsia and systolic blood pressure PGS in 2 prospective pregnancy cohorts with detailed phenotyping: the Fetal Medicine Foundation study (n=5207; 2127 cases) and the Pregnancy Outcome Prediction study (n=3659; 228 cases). Risk models included (1) clinical factors; (2) clinical factors plus PGS; (3) advanced model including first-trimester mean arterial pressure, PAPP-A (pregnancy-associated plasma protein-A), and uterine artery pulsatility index; and (4) advanced model plus PGS. Discriminative performance, measured by the area under the receiver operating characteristic curve, was assessed overall and by ancestry. RESULTS: The preeclampsia PGS was independently associated with preeclampsia (odds ratio per SD, 1.24 [95% CI, 1.17-1.31]; P<0.001). It modestly improved prediction over clinical models (area under the receiver operating characteristic curve 0.746 versus 0.750; P=0.017) but not over the advanced model (area under the receiver operating characteristic curve 0.817 versus 0.818; P=0.326). The systolic blood pressure PGS showed stronger performance, improving prediction over both models in women of European ancestry. No improvement was observed with either score in women of African ancestry. CONCLUSIONS: PGSs for preeclampsia and SBP provide modest added predictive value beyond clinical risk factors in European ancestry women. Limited utility in African ancestry women reflects underrepresentation in the genome-wide association studies used to develop current scores. As cohort sizes grow and models are refined, PGSs may become important tools for equitable risk stratification in maternal health.

Adult↗