A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
Douglas P. Wightman, Iris E. Jansen, Jeanne E. Savage, Alexey Shadrin, Shahram Bahrami, Dominic Holland, Arvid Rongve, Sigrid Børte, Bendik S. Winsvold, Ole Kristian Drange, Amy E. Martinsen, Anne Heidi Skogholt, Cristen J. Willer, Geir Bråthen, Ingunn Bosnes, Jonas B. Nielsen, Lars G. Fritsche, Laurent F. Thomas, Linda M. Pedersen, Maiken E. Gabrielsen, Marianne Bakke Johnsen, Tore Wergeland Meisingset, Wei Zhou, Petroula Proitsi, Angela Hodges, Richard Dobson, Latha Velayudhan, Karl Heilbron, Adam Auton, Michelle Agee, Stella Aslibekyan, Elizabeth Babalola, Robert K. Bell, Jessica Bielenberg, Katarzyna Bryc, Emily Bullis, Briana Cameron, Daniella Coker, Gabriel Cuéllar-Partida, Devika Dhamija, Sayantan Das, Sarah L. Elson, Teresa Filshtein, Kipper Fletez‐Brant, Pierre Fontanillas, Will Freyman, Pooja Gandhi, Barry Hicks, David A. Hinds, Karen E. Huber, Ethan M. Jewett, Yunxuan Jiang, Aaron Kleinman, Katelyn Kukar, Vanessa Lane, Keng‐Han Lin, Maya Lowe, Marie K. Luff, Jey C. McCreight, Matthew H. McIntyre, Kimberly F. McManus, Steven J. Micheletti, Meghan E. Moreno, Joanna L. Mountain, Sahar V. Mozaffari, Priyanka Nandakumar, Elizabeth S. Noblin, Jared O’Connell, Aaron A. Petrakovitz, G. David Poznik, Morgan Schumacher, Anjali J. Shastri, Janie F. Shelton, Jingchunzi Shi, Suyash Shringarpure, Chao Tian, Vinh Tran, Joyce Y. Tung, Xin Wang, Wei Wang, Catherine H. Weldon, Peter Wilton, Julia Sealock, Lea K. Davis, Nancy L. Pedersen, Chandra A. Reynolds, Ida Karlsson, Sigurður H. Magnússon, Hreinn Stefánsson, Steinunn Þórðardóttir, Pálmi V. Jónsson, Jón Snædal, Anna Zettergren, Ingmar Skoog, Silke Kern, Margda Wærn, Henrik Zetterberg, Kaj Blennow, Eystein Stordal, Kristian Hveem
Abstract
Late-onset Alzheimer's disease is a prevalent age-related polygenic disease that accounts for 50-70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer's disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer's disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer's disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer's disease to identify further genetic variants that contribute to Alzheimer's pathology.