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

Lennon, Niall J.; Kottyan, Leah C.; Kachulis, Christopher; Abul‐Husn, Noura S.; Arias, Joshua; Belbin, Gillian M.; Below, Jennifer E.; Berndt, Sonja I.; Chung, Wendy K.; Cimino, James J.; Clayton, Ellen Wright; Connolly, John J.; Crosslin, David R.; Dikilitas, Ozan; Edwards, Digna R. Velez; Feng, QiPing; Fisher, Marissa; Freimuth, Robert R.; Ge, Tian; Berndt, Sonja; Hirschhorn, Joel N.; Loos, Ruth J. F.; Glessner, Joseph; Gordon, Allan; Patterson, Candace; Håkonarson, Håkon; Harden, Maegan; Harr, Margaret; Hirschhorn, Joel N.; Hoggart, Clive; Hsu, Li; Irvin, Marguerite R.; Jarvik, Gail P.; Karlson, Elizabeth W.; Khan, Atlas; Khera, Amit V.; Kiryluk, Krzysztof; Kullo, Iftikhar J.; Larkin, Katie; Limdi, Nita A.; Linder, Jodell E.; Loos, Ruth J. F.; Luo, Yuan; Małolepsza, Edyta; Manolio, Teri A.; Martin, Lisa J.; McCarthy, L.R.; McNally, Elizabeth M.; Meigs, James B.; Mersha, Tesfaye B.; Mosley, Jonathan D.; Musick, Anjene; Namjou, Bahram; Pai, Nihal; Pesce, Lorenzo L.; Peters, Ulrike; Peterson, Josh F.; Prows, Cynthia A.; Puckelwartz, Megan J.; Rehm, Heidi L.; Roden, Dan M.; Rosenthal, Elisabeth A.; Rowley, Robb; Sawicki, Konrad Teodor; Schaid, Daniel J.; Smit, Roelof A. J.; Smith, Johanna L.; Smoller, Jordan W.; Thomas, Minta; Tiwari, Hemant K.; Toledo, Diana M.; Vaitinadin, Nataraja Sarma; Veenstra, David L.; Walunas, Theresa L.; Wang, Zhe; Wei, Wei‐Qi; Weng, Chunhua; Wiesner, Georgia L.; Yin, Xianyong; Kenny, Eimear E.

doi:10.1038/s41591-024-02796-z

articleNature MedicineFeb 1, 2024HYBRID OA

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

NJNiall J. Lennon LCLeah C. Kottyan CKChristopher Kachulis NSNoura S. Abul‐Husn JAJoshua Arias

Broad Institute · Cincinnati Children's Hospital Medical Center · +19 more institutions

PubMed

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Abstract

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…

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Topics & keywords

Topics

Keywords

Polygenic risk score
Pipeline (software)
Computer science
Selection (genetic algorithm)
Medicine
Machine learning
Biology

UN Sustainable Development Goals

Reduced inequalities

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