DNA analysis of genes (Polygenic risk) shows increased risk of 9 health problems (all 9 fought by Vitamin D)

Created July 2024

Selection, optimization and validation of ten chronic disease polygenic risk scores for clinical implementation in diverse US populations

Nature Medicine volume 30, pages 480–487 (2024) https://doi.org/10.1038/s41591-024-02796-z

Niall J. Lennon, Leah C. Kottyan, Christopher Kachulis, Noura S. Abul-Husn, Josh Arias, Gillian Belbin, Jennifer E. Below, Sonja I. Berndt, Wendy K. Chung, James J. Cimino, Ellen Wright Clayton, John J. Connolly, David R. Crosslin, Ozan Dikilitas, Digna R. Velez Edwards, QiPing Feng, Marissa Fisher, Robert R. Freimuth, Tian Ge, The GIANT Consortium, The All of Us Research Program, Joseph T. Glessner, Adam S. Gordon, Candace Patterson, …Eimear E. Kenny (80 authors)

100 to 1,000,000 gene SNPs

Varies of lot with race

Polygenic risk scores (PRSs) have improved in predictive performance, but several challenges remain to be addressed before PRSs can be implemented in the clinic, including reduced predictive performance of PRSs in diverse populations, and the interpretation and communication of genetic results to both providers and patients. To address these challenges, the National Human Genome Research Institute-funded Electronic Medical Records and Genomics (eMERGE) Network has developed a framework and pipeline for return of a PRS-based genome-informed risk assessment to 25,000 diverse adults and children as part of a clinical study. From an initial list of 23 conditions, ten were selected for implementation based on PRS performance, medical actionability and potential clinical utility, including cardiometabolic diseases and cancer. Standardized metrics were considered in the selection process, with additional consideration given to strength of evidence in African and Hispanic populations. We then developed a pipeline for clinical PRS implementation (score transfer to a clinical laboratory, validation and verification of score performance), and used genetic ancestry to calibrate PRS mean and variance, utilizing genetically diverse data from 13,475 participants of the All of Us Research Program cohort to train and test model parameters. Finally, we created a framework for regulatory compliance and developed a PRS clinical report for return to providers and for inclusion in an additional genome-informed risk assessment. The initial experience from eMERGE can inform the approach needed to implement PRS-based testing in diverse clinical settings.

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Various forms of PRSs are available to consumers through commercial platforms such as 23andMe, Myriad Genetics (riskScore), Allelica, Ambry Genetics, and others, and several noncommercial studies have explored the clinical use of PRSs in direct-to-participant models

Note: The word VITAMIN does not occur once in the study

Polygenic Risk Scores: Ready for Prime Time? (yes) Eric Topol Feb 2024

Polygenic Risk Scores: at 23andMe as of late 2023

Anxiety, Asthma, Atrial Fibrillation, Attention Deficit Hyperactivity Disorder (ADHD), Basal and Squamous Cell Carcinoma, Cat Allergy, Coronary Artery Disease, Diverticulitis, Dog Allergy, Eczema (Atopic Dermatitis), Fibromyalgia, Gallstones, Gestational Diabetes, Glaucoma, Gout, Hashimoto’s Disease, HDL Cholesterol, High Blood Pressure, Insomnia, Irritable Bowel Syndrome, Kidney Stones, LDL Cholesterol, Lupus, Melanoma, Migraine, Nearsightedness, Nonalcoholic Fatty Liver Disease, Obstructive Sleep Apnea, Panic Attacks, Polycystic Ovary Syndrome, Preeclampsia, Psoriasis, Restless Legs Syndrome, Rosacea, Seasonal Allergies, Severe Acne, Triglycerides, Uterine Fibroids