Returning integrated genomic risk and clinical recommendations: The eMERGE study

作者：Jodell E. Linder, Aimee Allworth, Harris T. Bland, Pedro J. Caraballo, Rex L. Chisholm, Ellen Wright Clayton, David R. Crosslin, Ozan Dikilitas, Alanna DiVietro, Edward D. Esplin, Sophie Forman, Robert R Freimuth, Adam S Gordon, Richard Green, Maegan Harden, Ingrid A. Holm, Gail P. Jarvik, Elizabeth W. Karlson, Sofia Labrecque, Niall J. Lennon, Nita A. Limdi, Kathleen F. Mittendorf, Shawn N. Murphy, Lori A. Orlando, Cynthia A. Prows, Luke V. Rasmussen, Laura J. Rasmussen‐Torvik, Robb Rowley, Konrad Teodor Sawicki, Tara Schmidlen, Shannon Terek, David L. Veenstra, Digna R. Velez Edwards, Devin Absher, Noura S. Abul‐Husn, Jorge Alsip, Hana Bangash, Mark Beasley, Jennifer E. Below, Eta S. Berner, James Booth, Wendy K. Chung, James J. Cimino, John J. Connolly, Patrick Davis, Beth Devine, Stephanie M. Fullerton, Candace Guiducci, Melissa L. Habrat, Heather S. Hain, Håkon Håkonarson, Margaret Harr, Eden Haverfield, Valentina Hernandez, Christin Hoell, Martha Horike‐Pyne, George Hripcsak, Marguerite R. Irvin, Christopher Kachulis, Dean Karavite, Eimear E. Kenny, Atlas Khan, Krzysztof Kiryluk, Bruce R. Korf, Leah C. Kottyan, Iftikhar J. Kullo, Katie Larkin, Cong Liu, Edyta Małolepsza, Teri A. Manolio, Thomas May, Elizabeth M. McNally, Frank Mentch, Alexandra Miller, Sean D Mooney, Priyanka Murali, Brenda Mutai, Naveen Muthu, Bahram Namjou, Emma Perez, Megan J. Puckelwartz, Tejinder Rakhra-Burris, Dan M. Roden, Elisabeth A. Rosenthal, Seyedmohammad Saadatagah, Maya Sabatello, Dan Schaid, Baergen I. Schultz, Lynn Seabolt, Gabriel Q. Shaibi, Richard R. Sharp, Brian Shirts, Maureen E. Smith, Jordan W. Smoller, Rene Sterling, Sabrina A. Suckiel, Jeritt G. Thayer, Hemant K. Tiwari, Susan Brown Trinidad, Theresa L. Walunas, Wei‐Qi Wei, Quinn S. Wells, Chunhua Weng, Georgia L. Wiesner, Ken Wiley, Adam Gordon, Agboade Sobowale, Aimee Allworth, Akshar Patel, Alanna DiVietro, Alanna Strong, Alborz Sherafati, Alborz Sherfati, Alex Bick, Alexandra Miller, Alka Chandel, Alyssa Rosenthal, Amit Khera, Amy Kontorovich, Andrew Beck, Andy Beck, Angelica Espinoza, Anna Lewis, Anya Prince, Atlas Khan, Ayuko Iverson, Bahram Namjou Khales, Barbara Benoit, Becca Hernan, Ben Kallman, Ben Kerman, Ben Shoemaker, Benjamin Satterfield, Beth Devine, Bethany Etheridge, Blake Goff, Bob Freimuth, Bob Grundmeier, Brenae Collier, Brenda Mutai, Brett Harnett, Brian Chang, Brian Piening, Brittney Davis, Bruce Korf, Candace Patterson, Carmen Demetriou, Casey Ta, Catherine Hammack, Catrina Nelson, Caytie Gascoigne, Chad Dorn, Chad Moretz, Chris Kachulis, Christie Hoell, Christine Cowles, Christoph Lange, Chunhua Weng, Cindy Prows, Cole Brokamp, Cong Liu, Courtney Scherr, Crystal Gonzalez, Cynthia Ramirez, Daichi Shimbo, Dan M. Roden, Daniel Schaid, Dave Kaufman, David Crosslin, David Kochan, David L. Veenstra, Davinder Singh, Dean Karavite, Debbie Abrams, Devin Absher, Digna R. Velez Edwards, Eden Haverfield, Eduardo Morales, Edward Esplin, Edyta Małolepsza, Ehsan Alipour, Eimear E. Kenny, Elisabeth Rosenthal, Eliza Duvall, Elizabeth McNally, Elizabeth Bhoj, Elizabeth Cohn, Elizabeth Hibler, Elizabeth Karlson, Ellen Wright Clayton, Emily Chesnut, Emily DeFranco, Emily Gallagher, Emily Soper, Emma Perez, Erin Cash, Eta Berner, Fei Wang, Firas Wehbe, Francisco Ricci, Frank Mentch, Gabriel Shaibi, Gail P. Jarvik, George Hahn, George Hripcsak, Georgia L. Wiesner, Gillian Belbin, Gio Davogustto, Girish Nadkarni, Haijun Qiu, Håkon Håkonarson, Hana Bangash, Hannah Beasley, Hao Liu, Heide Aungst, Hemant Tiwari, Hillary Duckham, Hope Thomas, Iftikhar Kullo, Ingrid A. Holm, Isabelle Allen, Iuliana Ionita-Laza, Jacklyn Hellwege, Jacob Petrzelka, Jacqueline Odgis, Jahnavi Narula, Jake Petrzelka, Jalpa Patel, James J. Cimino, James Meigs, James Snyder, Janet Olson, Janet Zahner, Jeff Pennington, Jen Pacheco, Jennifer Allen Pacheco, Jennifer Morse, Jeremy Corsmo, Jeritt G. Thayer, Jim Cimino, Jingheng Chen, Jocelyn Fournier, Jodell Jackson, Joe Glessner, Joel Pacyna, Johanna Smith, John J. Connolly, John Lynch, John Shelley, Jonathan Mosley, Jordan Nestor, Jordan Smoller, Jorge Alsip, Joseph Kannry, Joseph Sutton, Josh Peterson, Joshua Smith, Julia Galasso, Julia Smith, Julia Wynn, Justin Gundelach, Justin Starren, Karmel Choi, Kate Mittendorf, Katherine Anderson, Katherine Bonini, Kathleen Leppig, Kathleen Muenzen, Katie Larkin, Kelsey Stuttgen, Ken Wiley, Kenny Nguyen, Kevin Dufendach, Kiley Atkins, Konrad Teodor Sawicki, Kristjan Norland, Krzysztof Kiryluk, Laura Beskow, Laura J. Rasmussen‐Torvik, Leah C. Kottyan, Li Hsu, Lifeng Tian, Lisa Mahanta, Lisa Martin, Lisa Wang, Lizbeth Gomez, Lorenzo Thompson, Lori Orlando, Lucas Richter, Luke V. Rasmussen, Lynn Petukhova, Lynn Seabolt, Madison O’Brien, Maegan Harden, Malia Fullerton, Margaret Harr, Mark Beasley, Marta Guindo, Martha Horike, Martha Horike‐Pyne, Marwah Abdalla, Marwan Hamed, Mary Beth Terry, Mary Maradik, Matt Wyatt, Matthew Davis, Matthew Lebo, Maureen Smith, Maya del Rosario, Maya Sabatello, Meckenzie Behr, Meg Roy-Puckelwartz, Mel Habrat, Melanie Myers, Meliha Yetisgen, Merve Iris, Michael DaSilva, Michael Preuss, Michelle McGowan, Mingjian Shi, Minoli Perera, Minta Thomas, Mitch Elkind, Mohammad Abbass, Mohammad Saadatagah, Molly Hess, Molly Maradik, Nataraja “RJ” Vaitinadin, Nataraja Vaitinadin, Naveen Muthu, Neil Netherly, Niall J. Lennon, Ning Shang, Nita Limdi, Noah Forrest, Noheli Romero, Nora Robinson, Noura Abul-Husn, Omar Elsekaily, Ozan Dikilitas, Patricia Kovatch, Patrick Davis, Paul Appelbaum, Paul Francaviglia, Paul O’Reilly, Paulette Chandler, Pedro J. Caraballo, Peter Tarczy-Hornoch, Pierre Shum, Priya Marathe, Priyanka Murali, Qiping Feng, Quinn S. Wells, Rachel Atchley, Radhika Narla, Rene Barton, Rene Sterling, Rex L. Chisholm, Richard Green, Richard Sharp, Riki Peters, Rita Kukafka, Robb Rowley, Robert R Freimuth, Robert Green, Robert Winter, Roger Mueller, Ruth Loos, Ryan Irvin, Sabrina A. Suckiel, Sajjad Hussain, Samer Sharba, Sandy Aronson, Sarah Jones, Sarah Knerr, Scott Nigbur, Scott Weiss, Sean D Mooney, Shannon Terek, Sharon Aufox, Sharon Nirenberg, Shawn Murphy, Sheila O’Byrne, Shing Wang (Sam) Choi, Sienna Aguilar, S.T. Bland, Stefanie Rodrigues, Stephanie Ledbetter, Stephanie Rutledge, Stuart James Booth, Su Xian, Susan Brown Trinidad, Suzanne Bakken, Tara Schmidlen, Tejinder Rakhra-Burris, Teri A. Manolio, Tesfaye Mersha, Theresa Walunas, Thevaa Chandereng, Thomas May, Tian Ge, Todd Edwards, Tom Kaszemacher, Valentina Hernandez, Valerie Willis, Vemi Desai, Vimi Desai, Virginia Lorenzi, Vivian Gainer, Wei‐Qi Wei, Wendy K. Chung, Wu-Chen Su, Xiao Chang, Yiqing Zhao, Yuan Luo, Yufeng Shen, Josh F. Peterson · 发表于：Genetics in Medicine · 年份：2023 · DOI：10.1016/j.gim.2023.100006 · 被引用次数：125 · 研究领域：BRCA gene mutations in cancer、Genetic Associations and Epidemiology、Genomics and Rare Diseases

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, 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.