Returning integrated genomic risk and clinical recommendations: the eMERGE study.

In Genetics in medicine : official journal of the American College of Medical Genetics

PURPOSE : Assessing the risk of common, complex diseases requires consideration of clinical risk factors as well as monogenic and polygenic risks, which in turn may be reflected in family history. Returning risks to individuals and providers may influence preventive care or use of prophylactic therapies for those individuals at high genetic risk.

METHODS : To enable integrated genetic risk assessment, the eMERGE (electronic MEdical Records and GEnomics) network is enrolling 25,000 diverse individuals in a prospective cohort study across 10 sites. The network developed methods to return cross-ancestry polygenic risk scores (PRS), monogenic risks, family history, and clinical risk assessments via a Genome Informed Risk Assessment (GIRA) report and will assess uptake of care recommendations after return of results.

RESULTS : GIRAs include summary care recommendations for 11 conditions, education pages, and clinical laboratory reports. The return of high-risk GIRA to individuals and providers includes guidelines for care and lifestyle recommendations. Assembling the GIRA required infrastructure and workflows for ingesting and presenting content from multiple sources. Recruitment began in February 2022.

CONCLUSION : Return of a novel report for communicating monogenic, polygenic, and family history based risk factors will inform the benefits of integrated genetic risk assessment for routine health care.

Linder Jodell E, Allworth Aimee, Bland Sarah T, Caraballo Pedro J, Chisholm Rex L, Clayton Ellen Wright, Crosslin David R, Dikilitas Ozan, DiVietro Alanna, Esplin Edward D, Forman Sophie, Freimuth Robert R, Gordon Adam S, Green Richard, Harden Maegan V, Holm Ingrid A, Jarvik Gail P, Karlson Elizabeth W, Labrecque Sofia, Lennon Niall J, Limdi Nita A, Mittendorf Kathleen F, Murphy Shawn N, Orlando Lori, Prows Cynthia A, Rasmussen Luke V, Rasmussen-Torvik Laura, Rowley Robb, Sawicki Konrad Teodor, Schmidlen Tara, Terek Shannon, Veenstra David, Velez Edwards Digna R, Absher Devin, Abul-Husn Noura S, Alsip Jorge, Bangash Hana, Beasley Mark, Below Jennifer E, Berner Eta S, Booth James, Chung Wendy K, Cimino James J, Connolly John, Davis Patrick, Devine Beth, Fullerton Stephanie M, Guiducci Candace, Habrat Melissa L, Hain Heather, Hakonarson Hakon, Harr Margaret, Haverfield Eden, Hernandez Valentina, Hoell Christin, Horike-Pyne Martha, Hripcsak George, Irvin Marguerite R, Kachulis Christopher, Karavite Dean, Kenny Eimear E, Khan Atlas, Kiryluk Krzysztof, Korf Bruce, Kottyan Leah, Kullo Iftikhar J, Larkin Katie, Liu Cong, Malolepsza Edyta, Manolio Teri A, May Thomas, McNally Elizabeth M, Mentch Frank, Miller Alexandra, Mooney Sean D, Murali Priyanka, Mutai Brenda, Muthu Naveen, Namjou Bahram, Perez Emma F, Puckelwartz Megan J, Rakhra-Burris Tejinder, Roden Dan M, Rosenthal Elisabeth A, Saadatagah Seyedmohammad, Sabatello Maya, Schaid Dan J, Schultz Baergen, Seabolt Lynn, Shaibi Gabriel Q, Sharp Richard R, Shirts Brian, Smith Maureen E, Smoller Jordan W, Sterling Rene, Suckiel Sabrina A, Thayer Jeritt, Tiwari Hemant K, Trinidad Susan B, Walunas Theresa, Wei Wei-Qi, Wells Quinn S, Weng Chunhua, Wiesner Georgia L, Wiley Ken, Peterson Josh F

2023-Jan-06

common variants, family history, genotyping, monogenic risks, polygenic risk scores