Early risk identification and prevention of bipolar disorder: ethical considerations and user perspectives

Biological Psychiatry, Год журнала: 2025, Номер unknown

Опубликована: Янв. 1, 2025

Язык: Английский

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Dual exposure-by-polygenic score interactions highlight disparities across social groups in the proportion needed to benefit

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Июль 30, 2024

The transferability of polygenic scores across population groups is a major concern with respect to the equitable clinical implementation genomic medicine. Since genetic associations are identified relative mean, inevitably differences in disease or trait prevalence among social strata influence relationship between PGS and risk. Here we quantify magnitude PGS-by-Exposure (PGSxE) interactions for seven human diseases (coronary artery disease, type 2 diabetes, obesity thresholded body mass index waist-to-hip ratio, inflammatory bowel chronic kidney asthma) pairs 75 exposures White-British subset UK Biobank study (n=408,801). Across 24,198 PGSxE models, 746 (3.1%) were significant by two criteria, at least three-fold more than expected chance under each criterion. Predictive accuracy significantly improved high-risk including interaction terms effects as large those documented low ancestries. predominant mechanism PGS×E shown be amplification presence adverse such polyunsaturated fatty acids, mediators obesity, determinants ill health. We introduce notion proportion needed benefit (PNB) which cumulative number treat range show that typically this halved 70

Язык: Английский

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Multiancestry transferability of a polygenic risk score for diverticulitis

BMJ Open Gastroenterology, Год журнала: 2024, Номер 11(1), С. e001474 - e001474

Опубликована: Сен. 1, 2024

Objective Polygenic risk scores (PRS) for diverticular disease must be evaluated in diverse cohorts. We sought to explore shared genetic predisposition across the phenome and assess stratification individuals genetically similar European, African Admixed-American reference samples. Methods A 44-variant PRS was applied All of Us Research Program. Phenome-wide association studies (PheWAS) identified conditions linked with heightened susceptibility disease. To evaluate stratification, logistic regression models symptomatic severe diverticulitis were compared base covariates age, sex, body mass index, smoking principal components. Performance assessed using area under receiver operating characteristic curves (AUROC) Nagelkerke’s R 2 . Results The cohort comprised 181 719 PheWAS 50 037 modelling. associations disease, connective tissue hernias. Across ancestry groups, one SD increase consistently associated greater odds (range ORs (95% CI) 1.60 (1.27 2.02) 1.86 (1.42 2.42)) ((95% 1.27 (1.10 1.46) 1.66 (1.55 1.79)) relative controls. European achieved highest AUROC (AUROC 0.78 (0.75 0.81); 0.25). provided a maximum 0.034 modest improvement. Conclusion Associations between presentations persisted cohorts when controlling known factors. Relative improvements model performance observed, but absolute change magnitudes modest.

Язык: Английский

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Comparative Performance of Polygenic Risk Scores for Atherosclerotic Cardiovascular Disease Subtypes in the All of Us Research Program

medRxiv (Cold Spring Harbor Laboratory), Год журнала: 2024, Номер unknown

Опубликована: Ноя. 5, 2024

Abstract Background Performance and portability of contemporary polygenic risk scores (PRS) for atherosclerotic cardiovascular disease (ASCVD) phenotypes vary based on different methods, training data, trait ascertainment. Objectives We aimed to investigate performance PRS ASCVD subtypes: coronary heart (CHD), abdominal aortic aneurysm (AAA), ischemic stroke (IS), peripheral artery (PAD), using the All Us Workbench which provides access a large diverse cohort with phenotype whole genome sequence data. also developed evaluated multi-trait each subtype. Methods 4 traits related factors was compared across genetic ancestry groups in 245,388 participants. Genetic EUR, African (AFR), Admixed American (AMR), remaining (combined as Other, OTH) were defined by principal components. CHD, IS, AAA, PAD, (combining well factors) assessed hazard ratios (HR) per SD increase. Results For CHD PGS003725 performed best (HR 1 increase [95% CI]), (EUR: 1.72[1.67-1.78], AFR: 1.24[1.18-1.31], AMR: 1.48[1.37-1.59], OTH: 1.65[1.52-1.79]). The performing AAA PGS003972 1.68[1.59-1.78], 1.29[1.13-1.48], 1.30[1.06-1.60], 1.45[1.20-1.75]). IS PGS000039 AFR (1.12[1.06-1.17]), AMR (1.11[1.04-1.19]), OTH (1.23[1.09-1.38]), PGS004939 EUR (1.16[1.12-1.20]). PAD PGS004940 (1.26[1.22-1.30]), (1.11[1.05-1.18]), (1.08[1.01-1.16]), (1.13[1.04-1.22]). Multi-trait better than individual phenotype. Also, derived from multi-ancestry cohorts those single ancestry. Conclusions multiple ancestrally admixed individuals. PAD.

Язык: Английский

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Omics Studies in CKD: Diagnostic Opportunities and Therapeutic Potential

PROTEOMICS, Год журнала: 2024, Номер unknown

Опубликована: Ноя. 11, 2024

Omics technologies have significantly advanced the prediction and therapeutic approaches for chronic kidney disease (CKD) by providing comprehensive molecular insights. This is a review of current state future prospects integrating biomarkers into clinical practice CKD, aiming to improve patient outcomes targeted interventions. In fact, integration genomic, transcriptomic, proteomic, metabolomic data has enhanced our understanding CKD pathogenesis identified novel an early diagnosis treatment. Advanced computational methods artificial intelligence (AI) further refined multi-omics analysis, leading more accurate models progression responses. These developments highlight potential care with precise individualized treatment plan .

Язык: Английский

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Promises and pitfalls of preimplantation genetic testing for polygenic disorders: a narrative review

F&S Reviews, Год журнала: 2024, Номер 6(1), С. 100085 - 100085

Опубликована: Дек. 20, 2024

Язык: Английский

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