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Article|Articles in Press, 100006

Returning integrated genomic risk and clinical recommendations: the eMERGE study

Open AccessPublished:January 06, 2023DOI:https://doi.org/10.1016/j.gim.2023.100006
Returning integrated genomic risk and clinical recommendations: the eMERGE study
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      Abstract

      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.

      KEYWORDS

      Article info

      Publication history

      Accepted: December 21, 2022
      Received in revised form: December 16, 2022
      Received: July 26, 2022

      Publication stage

      In Press Accepted Manuscript

      Footnotes

      The eMERGE Consortium: 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 Roden, Daniel Schaid, Dave Kaufman, David Crosslin, David Kochan, David Veenstra, Davinder Singh, Dean Karavite, Debbie Abrams, Devin Absher, Digna Velez Edwards, Eden Haverfield, Eduardo Morales, Edward Esplin, Edyta Malolepsza, Ehsan Alipour, Eimear Kenny, Elisabeth Rosenthal, Eliza Duvall, Elizabeth McNally, Elizabeth Bhoj, Elizabeth Cohn, Elizabeth Hibler, Elizabeth Karlson, Elizabeth McNally, Ellen 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 Jarvik, George Hahn, George Hripcsak, Georgia Wiesner, Gillian Belbin, Gio Davogustto, Girish Nadkarni, Haijun Qiu, Hakon Hakonarson, Hana Bangash, Hannah Beasley, Hao Liu, Heide Aungst, Hemant Tiwari, Hillary Duckham, Hope Thomas, Iftikhar Kullo, Ingrid Holm, Isabelle Allen, Iuliana Ionita-Laza, Jacklyn Hellwege, Jacob Petrzelka, Jacqueline Odgis, Jahnavi Narula, Jake Petrzelka, Jalpa Patel, James Cimino, James Meigs, James Snyder, Janet Olson, Janet Zahner, Jeff Pennington, Jen Pacheco, Jennifer Allen Pacheco, Jennifer Morse, Jeremy Corsmo, Jeritt Thayer, Jim Cimino, Jingheng Chen, Jocelyn Fournier, Jodell Jackson, Joe Glessner, Joel Pacyna, Johanna Smith, John 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 Sawicki, Kristjan Norland, Krzysztof Kiryluk, Laura Beskow, Laura Rasmussen-Torvik, Leah Kottyan, Li Hsu, Lifeng Tian, Lisa Mahanta, Lisa Martin, Lisa Wang, Lizbeth Gomez, Lorenzo Thompson, Lori Orlando, Lucas Richter, Luke 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 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 Caraballo, Peter Tarczy-Hornoch, Pierre Shum, Priya Marathe, Priyanka Murali, Qiping Feng, Quinn Wells, Rachel Atchley, Radhika Narla, Rene Barton, Rene Sterling, Rex Chisholm, Richard Green, Richard Sharp, Riki Peters, Rita Kukafka, Robb Rowley, Robert Freimuth, Robert Green, Robert Winter, Roger Mueller, Ruth Loos, Ryan Irvin, Sabrina Suckiel, Sajjad Hussain, Samer Sharba, Sandy Aronson, Sarah Jones, Sarah Knerr, Scott Nigbur, Scott Weiss, Sean Mooney, Shannon Terek, Sharon Aufox, Sharon Nirenberg, Shawn Murphy, Sheila O'Byrne, Shing Wang (Sam) Choi, Sienna Aguilar, ST Bland, Stefanie Rodrigues, Stephanie Ledbetter, Stephanie Rutledge, Stuart James Booth, Su Xian, Susan Brown Trinidad, Suzanne Bakken, Tara Schmidlen, Tejinder Rakhra-Burris, Teri 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 Chung, Wu-Chen Su, Xiao Chang, Yiqing Zhao, Yuan Luo, Yufeng Shen.

      Conflicts of interest:

      The authors declare no conflict of interest except for the following individuals: Noura S. Abul-Husn is an employee and equity holder of 23andMe; serves as a scientific advisory board member for Allelica; received personal fees from Genentech, Allelica, and 23andMe; received research funding from Akcea; and was previously employed by Regeneron Pharmaceuticals. David R. Crosslin is a consultant for Optum Genomics and Chinook Therapeutics. Theresa Walunas has grant funding from Gilead Sciences. Lori Orlando and Tejinder Rakhra-Burris are founders of a company developing MeTree. Tara Schmidlen, Edward D. Esplin, and Eden Haverfield are employees and stockholders of Invitae. Elizabeth M. McNally has been a consultant for Avidity, Amgen, AstraZeneca, Cytokinetics, Invitae, Janssen, Pfizer, PepGen, Tenaya Therapeutics, Stealth BioTherapeutics; she is also the founder of Ikaika Therapeutics. Eimear E. Kenny received personal fees from Illumina, 23andMe, and Regeneron Pharmaceuticals, and serves as a scientific advisory board member for Encompass Bio, Foresite Labs, and Galateo Bio. Bruce Korf is an advisory board member and stockholder of GenomeMedical. Maya Sabatello is a member of the IRB of the All of Us Research Program. Emma F. Perez is a paid consultant for Allecia. Josh F. Peterson is a paid consultant for Natera.

      Identification

      DOI: https://doi.org/10.1016/j.gim.2023.100006

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      © 2023 Published by Elsevier Inc. on behalf of American College of Medical Genetics and Genomics.

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