A Type 1 Diabetes Genetic Risk Score Predicts Progression of Islet Autoimmunity and Development of Type 1 Diabetes in Individuals at Risk
Authors: Maria J. Redondo, Susan Geyer, Andrea K. Steck, Seth Sharp, John M. Wentworth, Michael N. Weedon, Peter Antinozzi, Jay Sosenko, Mark Atkinson, Alberto Pugliese, Richard A. Oram, P. Antinozzi, M. Atkinson, M. Battaglia, D. Becker, P. Bingley, E. Bosi, J. Buckner, P. Colman, P. Gottlieb, K. Herold, R. Insel, T. Kay, M. Knip, J.B. Marks, A. Moran, J. Palmer, M. Peakman, L. Philipson, A. Pugliese, P. Raskin, H. Rodriguez, B. Roep, W. Russell, D.A. Schatz, D. Wherrett, D. Wilson, W. Winter, A. Ziegler, C. Benoist, J. Blum, P. Chase, M. Clare-Salzler, R. Clynes, G. Eisenbarth, C.G. Fathman, G. Grave, B. Hering, F. Kaufman, E. Leschek, J. Mahon, K. Nanto-Salonen, G. Nepom, T. Orban, R. Parkman, M. Pescovitz, J. Peyman, M. Roncarolo, O. Simell, R. Sherwin, M. Siegelman, A. Steck, J. Thomas, M. Trucco, J. Wagner, , Carla J. Greenbaum, Katarzyna Bourcier, Richard Insel, Jeffrey P. Krischer, Ellen Leschek, Lisa Rafkin, Lisa Spain, Catherine Cowie, Mary Foulkes, Heidi Krause-Steinrauf, John M. Lachin, Saul Malozowski, John Peyman, John Ridge, Peter Savage, Jay S. Skyler, Stephanie J. Zafonte, Norma S. Kenyon, Irene Santiago, Jay M. Sosenko, Brian Bundy, Michael Abbondondolo, Timothy Adams, Darlene Amado, Ilma Asif, Matthew Boonstra, Brian Bundy, Cristina Burroughs, David Cuthbertson, Mary Deemer, Christopher Eberhard, Steve Fiske, Julie Ford, Jennifer Garmeson, Heather Guillette, Susan Geyer, Brian Hays, Courtney Henderson, Martha Henry, Kathleen Heyman, Belinda Hsiao, Christina Karges, Nichole Keaton, Amanda Kinderman, Pat Law, Ashely Leinbach, Cristin Linton, Shu Liu, Jennifer Lloyd, Jamie Malloy, Kristin Maddox, Julie Martin, Jessica Miller, Eric Milliot, Margaret Moore, Sarah Muller, Thuy Nguyen, Ryan O’Donnell, Vanessa Oduah, Jennifer Pilger, Amy Roberts, Kelly Sadler, Tina Stavros, Roy Tamura, Keith Wood, Ping Xu, Kenneth Young, Persida Alies, Franz Badias, Aaron Baker, Monica Bassi, Craig Beam, David Boulware, London Bounmananh, Susan Bream, Doug Freeman, Jessica Gough, Jinin Ginem, Moriah Granger, Mary Holloway, Michelle Kieffer, Page Lane, Lavanya Nallamshetty, Yazandra Parrimon, Kate Paulus, Joy Ramiro, AQesha Luvon Ritzie, Archana Sharma, Audrey Shor, Xiaohong Song, Amanda Terry, Jeanne Weinberger, Margaret Wootten, Pamela Harding, Susan McDonough, Paula F. McGee, Kimberly Owens Hess, Donna Phoebus, Scott Quinlan, Erica Raiden, Emily Batts, Chris Buddy, Kristin Kirpatrick, Mary Ramey, Ann Shultz, Chris Webb, Melita Romesco, Judith Fradkin, Emily Blumberg, Gerald Beck, David Brillon, Rose Gubitosi-Klug, Lori Laffel, Robert Veatch, Dennis Wallace, Jonathan Braun, Ake Lernmark, Bernard Lo, Herman Mitchell, Ali Naji, Jorn Nerup, Trevor Orchard, Michael Steffes, Anastasios Tsiatis, Bernard Zinman, Brett Loechelt, Lindsey Baden, Michael Green, Adriana Weinberg, Santica Marcovina, Jerry P. Palmer, Adriana Weinberg, Liping Yu, Sunanda Babu, William Winter, George S. Eisenbarth, Polly Bingley, Raphael Clynes, Linda DiMeglio, George Eisenbarth, Brian Hays, Jennifer Marks, Della Matheson, Henry Rodriguez, Darrell Wilson, Maria J. Redondo, David Gomez, Xiati Zheng, Sandra Pena, Massimo Pietropaolo, Emily Batts, Tyler Brown, Jane Buckner, Angela Dove, Marissa Hammond, Deborah Hefty, Jani Klein, Kristen Kuhns, McKenzie Letlau, Sandra Lord, Marli McCulloch-Olson, Lisa Miller, Gerald Nepom, Jared Odegard, Mary Ramey, Elaine Sachter, Marissa St. Marie, Kimberly Stickney, Dana VanBuecken, Ben Vellek, Christine Webber, Laurie Allen, Jenna Bollyk, Nicole Hilderman, Hebatullah Ismail, Steve Lamola, Srinath Sanda, Heather Vendettuoli, David Tridgell, Roshanak Monzavi, Meredith Bock, Lynda Fisher, Mary Halvorson, Debra Jeandron, Mimi Kim, Jamie Wood, Mitchell Geffner, Francine Kaufman, Robertson Parkman, Christine Salazar, Robin Goland, Raphael Clynes, Steve Cook, Matthew Freeby, Mary Pat Gallagher, Rachelle Gandica, Ellen Greenberg, Amy Kurland, Sarah Pollak, Amy Wolk, Mary Chan, Linda Koplimae, Elizabeth Levine, Kelly Smith, Jeniece Trast, Linda DiMeglio, Janice Blum, Carmella Evans-Molina, Robin Hufferd, Bonnie Jagielo, Christy Kruse, Vanessa Patrick, Mark Rigby, Maria Spall, Kim Swinney, Jennifer Terrell, Lyla Christner, LeeAnn Ford, Sheryl Lynch, Martha Menendez, Patricia Merrill, Mark Pescovitz, Henry Rodriguez, Cielo Alleyn, David Baidal, Steve Fay, Jason Gaglia, Brittany Resnick, Sarah Szubowicz, Gordon Weir, Ronald Benjamin, Debbie Conboy, Andrea deManbey, Richard Jackson, Heyam Jalahej, Tihmar Orban, Alyne Ricker, Joseph Wolfsdorf, Hui H. Zhang, Darrell Wilson, Tandy Aye, Bonita Baker, Karen Barahona, Bruce Buckingham, Kerry Esrey, Trudy Esrey, Garry Fathman, Radhika Snyder, Beenu Aneja, Maya Chatav, Oralia Espinoza, Eliana Frank, Jenny Liu, Jennifer Perry, Rebecca Pyle, Alison Rigby, Kristin Riley, Adriana Soto, Stephen Gitelman, Saleh Adi, Mark Anderson, Ashley Berhel, Kathy Breen, Kathleen Fraser, Andrea Gerard-Gonzalez, Paula Jossan, Robert Lustig, Sara Moassesfar, Amy Mugg, David Ng, Priya Prahalod, Martha Rangel-Lugo, Srinath Sanda, Joshua Tarkoff, Christine Torok, Rebecca Wesch, Ivy Aslan, Jeanne Buchanan, Jennifer Cordier, Celia Hamilton, Louise Hawkins, Thu Ho, Anjali Jain, Karen Ko, Theresa Lee, Shelly Phelps, Stephen Rosenthal, Taninee Sahakitrungruang, Lorraine Stehl, Lisa Taylor, Marcia Wertz, Jenise Wong, Louis Philipson, Rosemary Briars, Nancy Devine, Elizabeth Littlejohn, Tiffany Grant, Peter Gottlieb, Georgeanna Klingensmith, Andrea Steck, Aimon Alkanani, Kimberly Bautista, Ruth Bedoy, Aaron Blau, Betsy Burke, Laraine Cory, MyLinh Dang, Lisa Fitzgerald-Miller, Alex Fouts, Vicky Gage, Satish Garg, Patricia Gesauldo, Raymond Gutin, Cory Hayes, Michelle Hoffman, Kaitlin Ketchum, Nyla Logsden-Sackett, David Maahs, Laurel Messer, Lisa Meyers, Aaron Michels, Stesha Peacock, Marian Rewers, Perla Rodriguez, Flor Sepulbeda, Rachel Sippl, Andrea Steck, Iman Taki, Bao-Khan Tran, Tuan Tran, R. Paul Wadwa, Philip Zeitler, Jennifer Barker, Sandra Barry, Laurie Birks, Leah Bomsburger, Terra Bookert, Leah Briggs, Patricia Burdick, Rosio Cabrera, Peter Chase, Erin Cobry, Amy Conley, Gabrielle Cook, Joseph Daniels, Dominic DiDomenico, Jennifer Eckert, Angelica Ehler, George Eisenbarth, Pamela Fain, Rosanna Fiallo-Scharer, Nicole Frank, Hannah Goettle, Michelle Haarhues, Sherrie Harris, Lauren Horton, John Hutton, Joy Jeffrrey, Rachael Jenison, Kelly Jones, Whitney Kastelic, Maria Amelia King, Debbie Lehr, Jenna Lungaro, Kendra Mason, Heather Maurer, Luy Nguyen, Allison Proto, Jaime Realsen, Kristina Schmitt, Mara Schwartz, San Skovgaard, Jennifer Smith, Brandon Vanderwel, Mary Voelmle, Rebecca Wagner, Amy Wallace, Philip Walravens, Laurie Weiner, Becky Westerhoff, Emily Westfall, Katina Widmer, Hali Wright, Desmond Schatz, Annie Abraham, Mark Atkinson, Miriam Cintron, Michael Clare-Salzler, Jessica Ferguson, Michael Haller, Jennifer Hosford, Diane Mancini, Hank Rohrs, Janet Silverstein, Jamie Thomas, William Winter, Gloria Cole, Roberta Cook, Ryan Coy, Elena Hicks, Nancy Lewis, Jennifer Marks, Alberto Pugliese, Carlos Blaschke, Della Matheson, Natalia Sanders-Branca, Jay Sosenko, Luz Arazo, Ray Arce, Mario Cisneros, Samir Sabbag, Antoinette Moran, Carrie Gibson, Brian Fife, Bernhard Hering, Christine Kwong, Janice Leschyshyn, Brandon Nathan, Beth Pappenfus, Anne Street, Mary Ann Boes, Sarah Peterson Eck, Lois Finney, Theresa Albright Fischer, Andrea Martin, Chenai Jacqueline Muzamhindo, Missy Rhodes, Jennifer Smith, John Wagner, Bryan Wood, Dorothy Becker, Kelli Delallo, Ana Diaz, Barbara Elnyczky, Ingrid Libman, Beata Pasek, Karen Riley, Massimo Trucco, Brian Copemen, Diane Gwynn, Frederico Toledo, Henry Rodriguez, Sureka Bollepalli, Frank Diamond, Emily Eyth, Danielle Henson, Anne Lenz, Dorothy Shulman, Phillip Raskin, Soumya Adhikari, Brian Dickson, Erin Dunnigan, Ildiko Lingvay, Lourdes Pruneda, Maria Ramos-Roman, Philip Raskin, Chanhaeng Rhee, John Richard, Mark Siegelman, Daytheon Sturges, Kathryn Sumpter, Perrin White, Marilyn Alford, Jamie Arthur, M. Larissa Aviles-Santa, Erica Cordova, Renee Davis, Stefani Fernandez, Steve Fordan, Tauri Hardin, Aris Jacobs, Polina Kaloyanova, Ivanna Lukacova-Zib, Sasan Mirfakhraee, Alok Mohan, Hiroshi Noto, Oralenda Smith, Nenita Torres, Diane Wherrett, Diana Balmer, Lesley Eisel, Roze Kovalakovska, Mala Mehan, Farah Sultan, Brenda Ahenkorah, Jose Cevallos, Natasha Razack, Mary Jo Ricci, Angela Rhode, Mithula Srikandarajah, Rachel Steger, William E. Russell, Margo Black, Faith Brendle, Anne Brown, Daniel Moore, Eric Pittel, Alyssa Robertson, April Shannon, James W. Thomas, Kevan Herold, Laurie Feldman, Robert Sherwin, William Tamborlane, Stuart Weinzimer, Jorma Toppari, Tiina Kallio, Maarit Kärkkäinen, Elina Mäntymäki, Tiina Niininen, Birgitta Nurmi, Petro Rajala, Minna Romo, Sointu Suomenrinne, Kirsti Näntö-Salonen, Olli Simell, Tuula Simell, Emanuele Bosi, Manuela Battaglia, Eleonora Bianconi, Riccardo Bonfanti, Pauline Grogan, Andrea Laurenzi, Sabina Martinenghi, Franco Meschi, Matteo Pastore, Luca Falqui, Maria Teresa Muscato, Matteo Viscardi, Harriet Castleden, Nicola Farthing, Sam Loud, Claire Matthews, Jennifer McGhee, Ann Morgan, Joanna Pollitt, Rebecca Elliot-Jones, Carole Wheaton, Mikael Knip, Heli Siljander, Heli Suomalainen, Peter Colman, Felicity Healy, Shelley Mesfin, Leanne Redl, John Wentworth, Jinny Willis, Maree Farley, Leonard Harrison, Christine Perry, Fiona Williams, A. Mayo, J. Paxton, V. Thompson, L. Volin, C. Fenton, L. Carr, E. Lemon, M. Swank, M.K. Luidens, M. Salgam, V. Sharma, D. Schade, C. King, R. Carano, J. Heiden, N.D. Means, L. Holman, I. Thomas, D. Madrigal, T. Muth, C.L. Martin, C. Plunkett, C. Ramm, R.J. Auchus, W. Lane, E. Avots, M. Buford, C. Hale, J. Hoyle, B. Lane, A. Muir, S. Shuler, N. Raviele, E. Ivie, M. Jenkins, K. Lindsley, I. Hansen, D.O. Fadoju, E.I. Felner, B. Bode, R. Hosey, J. Sax, C. Jefferies, S. Mannering, R. Prentis, J.X. She, M. Stachura, D. Hopkins, J. Williams, L. Steed, E. Asatapova, S. Nunez, S. Knight, P. Dixon, J. Ching, T. Donner, S. Longnecker, K Abel, K. Arcara, S. Blackman, L. Clark, D. Cooke, L. Plotnick, P.A. Levin, L. Bromberger, K. Klein, K. Sadurska, C. Allen, D. Michaud, H. Snodgrass, G. Burghen, S. Chatha, C. Clark, J. Silverberg, C. Wittmer, J. Gardner, C. LeBoeuf, P. Bell, O. McGlore, H. Tennet, N. Alba, M. Carroll, L. Baert, H. Beaton, E. Cordell, A. Haynes, C. Reed, K. Lichter, P. McCarthy, S. McCarthy, T. Monchamp, J. Roach, S. Manies, F. Gunville, L. Marosok, T. Nelson, K. Ackerman, J. Rudolph, M. Stewart, K. McCormick, S. May, T. Falls, T. Barrett, K. Dale, L. Makusha, C. McTernana, K. Penny-Thomas, K. Sullivan, P. Narendran, J. Robbie, D. Smith, R. Christensen, B. Koehler, C. Royal, T. Arthur, H. Houser, J. Renaldi, S. Watsen, P. Wu, L. Lyons, B. House, J. Yu, H. Holt, M. Nation, C. Vickers, R. Watling, R. Heptulla, J. Trast, C. Agarwal, D.J. Newell, R. Katikaneni, C. Gardner, A. Del Rio, A. Logan, H. Collier, C. Rishton, G. Whalley, A. Ali, S. Ramtoola, T. Quattrin, L. Mastrandea, A.J. House, M. Ecker, C. Huang, C. Gougeon, J. Ho, D. Pacuad, D. Dunger, J. May, C. O’Brien, C. Acerini, B. Salgin, A. Thankamony, R. Williams, J. Buse, G. Fuller, M. Duclos, J. Tricome, H. Brown, D. Pittard, D. Bowlby, A. Blue, T. Headley, S. Bendre, K. Lewis, K. Sutphin, C. Soloranzo, J. Puskaric, H. Madison, M. Rincon, M. Carlucci, R. Shridharani, B. Rusk, E. Tessman, D.M. Huffman, H. Abrams, B. Biederman, M.D. Jones, V. Leathers, W. Brickman, P. Petrie, D. Zimmerman, J. Howard, L. Miller, R. Alemzadeh, D.V. Mihailescu, R. Melgozza-Walker, N. Abdulla, C. Boucher-Berry, D. Ize-Ludlow, R. Levy, C. Swenson Brousell, R. Scott, H. Heenan, H. Lunt, D. Kendall, J. Willis, B. Darlow, N. Crimmins, D. Edler, T. Weis, C. Schultz, D. Rogers, D. Latham, C. Mawhorter, C. Switzer, W. Spencer, P. Konstantnopoulus, S. Broder, J. Klein, B. Bachrach, M. Gardner, D. Eichelberger, L. Knight, L. Szadek, G. Welnick, B. Thompson, R. Hoffman, A. Revell, J. Cherko, K. Carter, E. Gilson, J. Haines, G. Arthur, B. Bowen, W.B. Zipf, P. Graves, R.A. Lozano, D. Seiple, K. Spicer, A. Chang, J. Fregosi, J. Harbinson, C. Paulson, S. Stalters, P. Wright, D. Zlock, A.E. Freeth, J. Victory, H. Maheshwari, A. Maheshwari, T. Holmstrom, J. Bueno, R. Arguello, J. Ahern, L. Noreika, V. Watson, S. Hourse, P. Breyer, C. Kissel, Y. Nicholson, M. Pfeifer, S. Almazan, J. Bajaj, M. Quinn, K. Funk, J. McCance, E. Moreno, R. Veintimilla, A. Wells, J. Cook, S. Trunnel, D. Transue, J. Surhigh, D. Bezzaire, K. Moltz, E. Zacharski, J. Henske, S. Desai, K. Frizelis, F. Khan, R. Sjoberg, K. Allen, P.P. Manning, G. Hendry, B. Taylor, S. Jones, R. Couch, R. Danchak, D. Lieberman, W. Strader, M.E. Bencomo, T. Bailey, L. Bedolla, C. Roldan, C. Moudiotis, B. Vaidya, C. Anning, S. Bunce, S. Estcourt, E. Folland, E. Gordon, C. Harrill, J. Ireland, J. Piper, L. Scaife, K. Sutton, S. Wilkins, M. Costelloe, J. Palmer, L. Casas, C. Miller, M. Burgard, C. Erickson, J. Hallanger-Johnson, P. Clark, W. Taylor, J. Galgani, S. Banerjee, C. Banda, D. McEowen, R. Kinman, A. Lafferty, S. Gillett, C. Nolan, M. Pathak, L. Sondrol, T. Hjelle, S. Hafner, J. Kotrba, R. Hendrickson, A.P. Cemeroglu, T. Symington, M. Daniel, Y. Appiagyei-Dankah, D.C. Postellon, M.S. Racine, L. Kleis, K. Barnes, S.E. Godwin, H. McCullough, K. Shaheen, G. Buck, L. Noel, M.L. Warren, S. Weber, S.M. Parker, I. Gillespie, B.A. Nelson, C. Frost, J. Amrhein, E.C. Moreland, A. Hayes, J. Peggram, J. Aisenberg, M.E. Riordan, J. Zasa, E. Cummings, K. Scott, T. Pinto, A. Mokashi, K. McAssey, E. Helden, P. Hammond, L. Dinning, S. Rahman, S. Ray, C. Dimicri, S. Guppy, H. Nielsen, C.K. Vogel, C. Ariza, L. Morales, Y.T. Chang, R.A. Gabbay, L. Ambrocio, L. Manley, R. Nemery, W. Charlton, P. Smith, L. Kerr, B. Steindel-Kopp, M. Alamaguer, E. Tabisola-Nuesca, A. Pendersen, N. Larson, H. Cooper-Olviver, D. Chan, D. Fitz-Patrick, T. Carreira, Y. Park, R. Ruhaak, D. Liljenquist, G. Browning, T. Coughenour, M.B. Sulk, E. Tsalikan, M. Tansey, J. Cabbage, N. Dixit, S. Pasha, M. King, K. Adcock, H. Atterberry, L. Fox, K. Englert, N. Mauras, J. Permuy, K. Sikes, T. Berhe, B. Guendling, L. McLennan, L. Paganessi, C. Murphy, M.B. Draznin, M. Kamboj, S. Sheppard, V. Lewis, L. Coates, W. Moore, G. Babar, J. Bedard, D. Brenson-Hughes, J. Cernich, M. Clements, R. Duprau, S. Goodman, L. Hester, L. Huerta-Saenz, A. Karmazin, T. Letjen, S. Raman, D. Morin, W. Bestermann, E.J. Morawski, J.L. White, A. Brockmyer, R. Bays, S. Campbell, A. Stapleton, N. Stone, A. Donoho, H. Everett, H. Hensley, M. Johnson, C. Marshall, N. Skirvin, P. Taylor, R. Williams, L. Ray, C. Wolverton, D.A. Nickels, C. Dothard, P.W. Speiser, M. Pellizzari, L. Bokor, K. Izuora, S. Abdelnour, P. Cummings, S. Paynor, M. Leahy, M. Riedl, S. Shockley, R. Saad, T. Briones, S. Casella, C. Herz, K. Walsh, J. Greening, F. Hay, S. Hunt, N. Sikotra, L. Simons, D.G. Karounos, R. Oremus, L. Dye, L. Myers, D. Ballard, W. Miers, R. Sparks, K.M. Thraikill, K. Edwards, J. Fowlkes, S. Kemp, A. Morales, L. Holland, L. Johnson, P. Paul, A. Ghatak, K. Phelen, H. Leyland, T. Henderson, D. Brenner, E. Oppenheimer, I. Mamkin, C. Moniz, C. Clarson, M. Lovell, A. Peters, V. Ruelas, D. Borut, D. Burt, M. Jordan, S. Castilla, P. Flores, M. Ruiz, L. Hanson, J. Green-Blair, R.J. Sheridan, K.A. Wintergerst, G. Pierce, A. Omoruyi, M. Foster, S. Kingery, A. Lunsford, I. Cervantes, T. Parker, P. Price, J. Urben, I. Doughty, H. Haydock, V. Parker, P. Bergman, S. Duncum, C. Rodda, A.D. Thomas, R. Ferry, D. McCommon, J. Cockroft, A. Perelman, R. Calendo, C. Barrera, E. Arce-Nunez, Y. Martinez, M. De la Portilla, I. Cardenas, L. Garrido, M. Villar, R. Lorini, E. Calandra, G. D’Annuzio, K. Perri, N. Minuto, C. Rebora, R. Callegari, O. Ali, J. Kramer, B. Auble, S. Cabrera, P. Donohoue, R. Fiallo-Scharer, M. Hessner, P. Wolfgram, A. Kansra, N. Bettin, R. McCuller, A. Miller, S. Accacha, J. Corrigan, E. Fiore, R.L. Levine, T.A. Mahoney, C. Polychronakos, V. Gagne, H. Starkman, M. Fox, D. Chin, F. Melchionne, L.A. Silverman, I. Marshall, L. Cerracchio, J. Cruz, A. Viswanathan, J. Wilson, S. Chalew, S. Valley, S. Layburn, A. Lala, P. Clesi, M. Genet, G. Uwaifo, A. Charron, T. Allerton, W. Cefalu, L. Melendez-Ramirez, R. Richards, C. Alleyn, E. Gustafson, M. Lizanna, J. Wahlen, S. Aleiwe, M. Hansen, H. Wahlen, C.J. Levy, A. Bonaccorso, R. Rapaport, Y. Tomer, D. Chia, M. Goldis, L. Iazzetti, M. Klein, C. Levister, L. Waldman, E. Wallach, M.O. Regelmann, Z. Antal, M. Aranda, C. Reynholds, N. Leech, D. Wake, C. Owens, M. Burns, J. Wotherspoon, A. Murray, K. Short, G. Curry, S. Kelsey, J. Lawson, J. Porter, S. Stevens, E. Thomson, S. Winship, L. Wynn, E. Wiltshire, J. Krebs, P. Cresswell, H. Faherty, C. Ross, A. Vinik, P. Barlow, M. Bourcier, M.L. Nevoret, J. Couper, S. Beresford, N. Thalagne, H. Roper, J. Gibbons, J. Hill, S. Balleaut, C. Brennan, J. Ellis-Gage, L. Fear, T. Gray, L. Jones, C. McNerney, L. Pointer, N. Price, K. Few, D. Tomlinson, L. Denvir, J. Drew, T. Randell, P. Mansell, S.A. Bell, S. Butler, Y. Hooton, H. Navarra, A. Roper, G. Babington, L. Crate, H. Cripps, A. Ledlie, C. Moulds, R. Norton, B. Petrova, O. Silkstone, C. Smith, K. Ghai, M. Murray, V. Viswanathan, M. Henegan, O. Kawadry, J.A. Olson, L. Patterson, T. Ahmad, B. Flores, D. Domek, S. Domek, K. Copeland, M. George, J. Less, T. Davis, M. Short, A. Dwarakanathan, P. O’Donnell, B. Boerner, L. Larson, M. Phillips, M. Rendell, K. Larson, C. Smith, K. Zebrowski, L. Kuechenmeister, M. Thevarayapillai, M. Daniels, H. Speer, N. Forghani, R. Quintana, C. Reh, A. Bhangoo, P. Desrosiers, L. Ireland, T. Misla, C. Torres, S. Wells, J. Villar, M. Yu, D. Berry, D. Cook, J. Soder, A. Powell, M. Ng, M. Morrison, Z. Haslam, M. Lawson, B. Bradley, J. Courtney, C. Richardson, C. Watson, E. Keely, D. DeCurtis, M. Vaccarcello-Cruz, Z. Torres, K. Sandberg, H. Hsiang, B. Joy, D. McCormick, A. Powell, H. Jones, J. Bell, S. Hargadon, S. Hudson, M. Kummer, S. Sauder, E. Sutton, K. Gensel, R. Aguirre-Castaneda, V. Benavides Lopez, D. Hemp, S. Allen, J. Stear, E. Davis, T. Jones, A. Roberts, J.A. Dart, N. Paramalingam, L.E. Levitt Katz, N. Chaudhary, K.M. Murphy, S.M. Willi, B. Schwartzman, C. Kapadia, D. Larson, D. McClellan, G. Shaibai, L.A. Kelley, G. Villa, C. Kelley, R. Diamond, M. Kabbani, T. Dajani, F. Hoekstra, M. Magorno, J. Holst, V. Chauhan, N. Wilson, P. Bononi, M. Sperl, A. Millward, M. Eaton, L. Dean, J. Olshan, H. Renna, C. Milliard, D. Snyder, S. Beaman, K. Burch, J. Chester, A. Ahmann, B. Wollam, D. DeFrang, R. Fitch, K. Jahnke, K. Hanavan, B. Klopfenstein, L. Nicol, R.W. Bergstrom, T. Noland, J. Brodksy, L. Bacon, J.B. Quintos, L.S. Topor, S. Bialo, B. Bancroft, A.G. Soto, W. Lagarde, H. Lockemer, T. Vanderploeg, M.A. Ibrahim, M. Huie, V. Sanchez, R. Edelen, R. Marchiando, J. Palmer, T. Repas, M. Wasson, P. Auker, J. Culbertson, T. Kieffer, D. Voorhees, T. Borgwardt, L. DeRaad, K. Eckert, E. Isaacson, H. Kuhn, A. Carroll, M. Schubert, G. Francis, S. Hagan, T. Le, M. Penn, E. Wickham, C. Leyva, K. Rivera, J. Padilla, I. Rodriguez, N. Jospe, J. Czyzyk, B. Johnson, U. Nadgir, N. Marlen, G. Prakasam, C. Rieger, N. Glaser, E.C. Heiser, B. Harris, C. Foster, H. Slater, K. Wheeler, D.L. Donaldson, M. Murray, D.E. Hale, R. Tragus, D.R. Word, J. Lynch, L. Pankratz, W. Rogers, R. Newfield, S. Holland, M. Hashiguchi, M. Gottschalk, A. Philis-Tsimikas, R. Rosal, S. Franklin, S.M. Guardado, N. Bohannon, M. Garcia, T. Aguinaldo, J. Phan, V. Barraza, D. Cohen, J. Pinsker, U. Khan, J. Wiley, L. Jovanovic, P. Misra, M. Wright, D. Cohen, K. Huang, M. Skiles, S. Maxcy, C. Pihoker, K. Cochrane, J. Fosse, S. Kearns, M. Klingsheim, N. Wright, L. Viles, H. Smith, S. Heller, M. Cunningham, A. Daniels, L. Zeiden, J. Field, R. Walker, K.J. Griffin, L. Bartholow, C. Erickson, J. Howard, B. Krabbenhoft, C. Sandman, A. Vanveldhuizen, J. Wurlger, A. Zimmerman, K. Hanisch, L. Davis-Keppen, A. Cotterill, J. Kirby, M. Harris, A. Schmidt, C. Kishiyama, C. Flores, J. Milton, W. Martin, C. Whysham, A. Yerka, T. Freels, J.M. Hassing, J. Webster, R. Green, P. Carter, J. Galloway, D. Hoelzer, S. Roberts, S. Said, P. Sullivan, H.F. Allen, E. Reiter, E. Feinberg, C. Johnson, L.A. Newhook, D. Hagerty, N.H. White, L. Levandoski, J. Kyllo, M. Johnson, C. Benoit, P. Iyer, F. Diamond, H. Hosono, S. Jackman, L. Barette, P. Jones, I. Sills, S. Bzdick, J. Bulger, R. Weinstock, I. Douek, R. Andrews, G. Modgill, G. Gyorffy, L. Robin, N. Vaidya, S. Crouch, K. O’Brien, C. Thompson, N. Thorne, J. Blumer, J. Kalic, L. Klepek, J. Paulett, B. Rosolowski, J. Horner, M. Watkins, J.L. Casey, K. Carpenter, C. Burns, J. Horton, C. Pritchard, D. Soetaert, A.G. Wynne, K. Kaiserman, M. Halvorson, C. Chin, O.Y. Molina, C. Patel, R. Senguttuvan, M. Wheeler, O. Furet, C. Steuhm, D.H. Jelley, S. Goudeau, L. Chalmers, D. Greer, C. Panagiotopoulos, D.L. Metzger, D. Nguyen, M. Horowitz, M.P. Christiansen, E. Glades, C. Morimoto, M. Macarewich, R. Norman, K. Patin, C. Vargas, A. Barbanica, A. Yu, P. Vaidyanathan, W. Osborne, R. Mehra, S. Kaster, S. Neace, J. Horner, G. Reeves, C. Cordrey, L. Marrs, T. Miller, S. Dowshen, D. Doyle, S. Walker, D. Catte, H. Dean, M. Drury-Brown, B. Hackman, M.M.C. Lee, S. Malkani, K. Cullen, K. Johnson, P. Hampton, M. McCarrell, C. Curtis, E. Paul, Y. Zambrano
Journal: Diabetes Care (2018)

OBJECTIVE We tested the ability of a type 1 diabetes (T1D) genetic risk score (GRS) to predict progression of islet autoimmunity and T1D in at-risk individuals. RESEARCH DESIGN AND METHODS We studied the 1,244 TrialNet Pathway to Prevention study participants (T1D patients’ relatives without diabetes and with one or more positive autoantibodies) who were genotyped with Illumina ImmunoChip (median [range] age at initial autoantibody determination 11.1 years [1.2–51.8], 48% male, 80.5% non-Hispanic white, median follow-up 5.4 years). Of 291 participants with a single positive autoantibody at screening, 157 converted to multiple autoantibody positivity and 55 developed diabetes. Of 953 participants with multiple positive autoantibodies at screening, 419 developed diabetes. We calculated the T1D GRS from 30 T1D-associated single nucleotide polymorphisms. We used multivariable Cox regression models, time-dependent receiver operating characteristic curves, and area under the curve (AUC) measures to evaluate prognostic utility of T1D GRS, age, sex, Diabetes Prevention Trial–Type 1 (DPT-1) Risk Score, positive autoantibody number or type, HLA DR3/DR4-DQ8 status, and race/ethnicity. We used recursive partitioning analyses to identify cut points in continuous variables. RESULTS Higher T1D GRS significantly increased the rate of progression to T1D adjusting for DPT-1 Risk Score, age, number of positive autoantibodies, sex, and ethnicity (hazard ratio [HR] 1.29 for a 0.05 increase, 95% CI 1.06–1.6; P = 0.011). Progression to T1D was best predicted by a combined model with GRS, number of positive autoantibodies, DPT-1 Risk Score, and age (7-year time-integrated AUC = 0.79, 5-year AUC = 0.73). Higher GRS was significantly associated with increased progression rate from single to multiple positive autoantibodies after adjusting for age, autoantibody type, ethnicity, and sex (HR 2.27 for GRS &amp;gt;0.295, 95% CI 1.47–3.51; P = 0.0002). CONCLUSIONS The T1D GRS independently predicts progression to T1D and improves prediction along T1D stages in autoantibody-positive relatives.