The Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores
Madeline L. Page, Elizabeth Vance, Matthew Cloward, Ed Ringger, Louisa Dayton, Mark Ebbert, The Alzheimer’s Disease Neuroimaging Initiative, Principal Investigator, Myron Weiner, Paul Aisen, Rebecca A. Petersen, Clifford R. Jack, William J. Jagust, John Q. Trojanowki, Arthur W. Toga, Laurel Beckett, R. C. Green, Andrew J. Saykin, Julia Morris, Richard J. Perrin, L. M. Shaw, ADNI External Advisory Board (ESAB), Zaven S. Khachaturian, María C. Carrillo, William Z. Potter, Lisa L. Barnes, Manon Bernard, Héctor M. González, Calvin Wai-Loon Ho, John Hsiao, Jacqueline M Jackson, Eliezer Masliah, D. Masterman, Ozioma C. Okonkwo, Richard J. Perrin, Louise Ryan, Jonathan I. Silverberg, ADNI 3 Private Partner Scientific Board (PPSB), A. Fleisher, D. T. Sacrey, Juliet Fockler, Costanza Conti, Dallas P. Veitch, John Neuhaus, Chongyao Jin, Rachel L. Nosheny, Miriam T. Ashford, Derek Flenniken, Adrieene Kormos, T. Monine, Michael S. Rafii, Rajiv Raman, Gustavo Jiménez, Michael Donohue, Devon Gessert, Joel Salazar, Christina Zimmerman, Yuliana Cabrera, Sarah Walter, Gabrielle Miller, G. Coker, T. Clanton, Lindsey Hergesheimer, Samuel Pattillo Smith, Oluwatoyin Adegoke, P. Mahboubi, Scott D. Moore, J. Pizzola, E. Shaffer, B. Sloan, Biostatistics Core Leaders and Key Personnel, Danielle Harvey, MRI Core Leaders and Key Personnel, Arivn Forghanian-Arani, Bret Borowski, Chad Ward, Charlotte Schwarz, David T. Jones, J Günter, Kejal Kantarci, Matthew L. Senjem, Prashanthi Vemuri, Ronald E. Reid, Nick C. Fox, Ian B. Malone, Pamela J. Thompson, Sophia I. Thomopoulos, Talia M. Nir, Neda Jahanshad, Charles DeCarli, Alex Knaack, E. Fletcher, D. Tosun-Turgut, S. R. Chen, Mi Kyung Choe, Karen Crawford, Paul A. Yushkevich, Sayantan Das, PET Core Leaders and Key Personnel, Robert A. Koeppe
Abstract
The process of identifying suitable genome-wide association (GWA) studies and formatting the data to calculate multiple polygenic risk scores on a single genome can be laborious. Here, we present a centralized polygenic risk score calculator currently containing over 250,000 genetic variant associations from the NHGRI-EBI GWAS Catalog for users to easily calculate sample-specific polygenic risk scores with comparable results to other available tools. Polygenic risk scores are calculated either online through the Polygenic Risk Score Knowledge Base (PRSKB; https://prs.byu.edu ) or via a command-line interface. We report study-specific polygenic risk scores across the UK Biobank, 1000 Genomes, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), contextualize computed scores, and identify potentially confounding genetic risk factors in ADNI. We introduce a streamlined analysis tool and web interface to calculate and contextualize polygenic risk scores across various studies, which we anticipate will facilitate a wider adaptation of polygenic risk scores in future disease research.