Association of Polygenic Risk Scores for Hearing Difficulty in Older Adults With Hearing Loss in Mid-Childhood and Midlife: A Population-Based Cross-sectional Study Within the Longitudinal Study of Australian Children.
Jing Wang et al. JAMA otolaryngology-- head & neck surgery 2023 1
This population-based cross-sectional study, including 1608 children and 1642 adults, nested within the Longitudinal Study of Australian Children found that in contemporaneous population-based samples, PRSs computed from self-reported hearing difficulty in 40- to 69-year-old adults showed some evidence of association with hearing ability in 11- to 12-year-olds and their parents, but minimal evidence of associations with speech reception ability.
Risk assessment for colorectal cancer via polygenic risk score and lifestyle exposure: a large-scale association study of East Asian and European populations.
Junyi Xin et al. Genome medicine 2023 1 (1) 4
Using the UK Biobank cohort, we further validated a significant dose-response effect of PRSCSx on incident colorectal cancer, in which the risk was 2.11- and 3.88-fold higher in individuals with intermediate and high PRSCSx than in the low score subgroup (Ptrend = 8.15 × 10-53). Notably, the detrimental effect of being at a high genetic risk could be largely attenuated by adherence to a favorable lifestyle, with a 0.53% reduction in 5-year absolute risk.
Genome-wide meta-analysis identifies 93 risk loci and enables risk prediction equivalent to monogenic forms of venous thromboembolism.
Ghouse Jonas et al. Nature genetics 2023 1
We report a genome-wide association study of venous thromboembolism (VTE) incorporating 81,190?cases and 1,419,671?controls sampled from six cohorts. We identify 93?risk loci, of which 62 are previously unreported. Many of the identified risk loci are at genes encoding proteins with functions converging on the coagulation cascade or platelet function. A VTE polygenic risk score (PRS) enabled effective identification of both high- and low-risk individuals.
Prioritizing the detection of rare pathogenic variants in population screening.
Lacaze Paul et al. Nature reviews. Genetics 2023 1
Population genomic screening to detect carriers of rare monogenic variants for medically actionable conditions is supported by substantial evidence of clinical utility and cost effectiveness. Much less evidence supports screening by polygenic risk scores, which do not detect rare variants. Using only polygenic scores in population screening initiatives, while ignoring the detection of higher-risk rare monogenic variants, is ill-advised.