The Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores

Madeline L Page; Elizabeth L Vance; Matthew E Cloward; Ed Ringger; Louisa Dayton; Mark T W Ebbert; Alzheimer’s Disease Neuroimaging Initiative; Justin B Miller; John S K Kauwe

doi:10.1038/s42003-022-03795-x

The Polygenic Risk Score Knowledge Base offers a centralized online repository for calculating and contextualizing polygenic risk scores

Commun Biol. 2022 Sep 2;5(1):899. doi: 10.1038/s42003-022-03795-x.

Authors

Collaborators

Alzheimer’s Disease Neuroimaging Initiative:
M W Weiner, P Aisen, R Petersen, C R Jack Jr, W Jagust, J Q Trojanowki, A W Toga, L Beckett, R C Green, A J Saykin, J C Morris, R J Perrin, L M Shaw, Z Khachaturian, M Carrillo, W Potter, L Barnes, M Bernard, H González, C Ho, J K Hsiao, J Jackson, E Masliah, D Masterman, O Okonkwo, R Perrin, L Ryan, N Silverberg, A Fleisher, D T Sacrey, J Fockler, C Conti, D Veitch, J Neuhaus, C Jin, R Nosheny, M Ashford, D Flenniken, A Kormos, T Monine, M Rafii, R Raman, G Jimenez, M Donohue, D Gessert, J Salazar, C Zimmerman, Y Cabrera, S Walter, G Miller, G Coker, T Clanton, L Hergesheimer, S Smith, O Adegoke, P Mahboubi, S Moore, J Pizzola, E Shaffer, B Sloan, D Harvey, A Forghanian-Arani, B Borowski, C Ward, C Schwarz, D Jones, J Gunter, K Kantarci, M Senjem, P Vemuri, R Reid, N C Fox, I Malone, P Thompson, S I Thomopoulos, T M Nir, N Jahanshad, C DeCarli, A Knaack, E Fletcher, D Tosun-Turgut, S R Chen, M Choe, K Crawford, P A Yushkevich, S Das, R A Koeppe, E M Reiman, K Chen, C Mathis, S Landau, N J Cairns, E Householder, E Franklin, H Bernhardt, L Taylor-Reinwald, L M Shaw, J Q Tojanowki, M Korecka, M Figurski, K Crawford, S Neu, K Nho, S L Risacher, L G Apostolova, L Shen, T M Foroud, K Nudelman, K Faber, K Wilmes, M W Winer, L Thal, J K Hsiao, L C Silbert, B Lind, R Crissey, J A Kaye, R Carter, S Dolen, J Quinn, L S Schneider, S Pawluczyk, M Becerra, L Teodoro, K Dagerman, B M Spann, J Brewer, H Vanderswag, A Fleisher, J Ziolkowski, J L Heidebrink, L Zbizek-Nulph, J L Lord, S S Mason, C S Albers, D Knopman, K Johnson, J Villanueva-Meyer, V Pavlik, N Pacini, A Lamb, J S Kass, R S Doody, V Shibley, M Chowdhury, S Rountree, M Dang, Y Stern, L S Honig, A Mintz, B Ances, D Winkfield, M Carroll, G Stobbs-Cucchi, A Oliver, M L Creech, M A Mintun, S Schneider, D Geldmacher, M N Love, R Griffith, D Clark, J Brockington, D Marson, H Grossman, M A Goldstein, J Greenberg, E Mitsis, R C Shah, M Lamar, P Samuels, R Duara, M T Greig-Custo, R Rodriguez, M Albert, C Onyike, L Farrington, S Rudow, R Brichko, S Kielb, A Smith, B A Raj, K Fargher, M Sadowski, T Wisniewski, M Shulman, A Faustin, J Rao, K M Castro, A Ulysse, S Chen, M O Sheikh, J Singleton-Garvin, P M Doraiswamy, J R Petrella, O James, T Z Wong, S Borges-Neto, J H Karlawish, D A Wolk, S Vaishnavi, C M Clark, S E Arnold, C D Smith, G A Jicha, R E Khouli, F D Raslau, O L Lopez, M Oakley, D M Simpson, A P Porsteinsson, K Martin, N Kowalski, M Keltz, B S Goldstein, K M Makino, M S Ismail, C Brand, G Thai, A Pierce, B Yanez, E Sosa, M Witbracht, B Kelley, T Nguyen, K Womack, D Mathews, M Quiceno, A I Levey, J J Lah, I Hajjar, J S Cellar, J M Burns, R H Swerdlow, W M Brooks, D H S Silverman, S Kremen, L Apostolova, K Tingus, P H Lu, G Bartzokis, E Woo, E Teng, N R Graff-Radford, F Parfitt, K Poki-Walker, M R Farlow, A M Hake, B R Matthews, J R Brosch, S Herring, C H van Dyck, A P Mecca, S P Good, M G MacAvoy, R E Carson, P Varma, H Chertkow, S Vaitekunis, C Hosein, S Black, B Stefanovic, C Heyn, G R Hsiung, E Kim, B Mudge, V Sossi, H Feldman, M Assaly, E Finger, S Pasternak, I Rachinsky, A Kertesz, D Drost, J Rogers, I Grant, B Muse, E Rogalski, J Robson, M Mesulam, D Kerwin, C Wu, N Johnson, K Lipowski, S Weintraub, B Bonakdarpour, N Pomara, R Hernando, A Sarrael, H J Rosen, B L Miller, D Perry, R S Turner, K Johnson, B Reynolds, K McCann, J Poe, R A Sperling, K A Johnson, G A Marshall, J Yesavage, J L Taylor, S Chao, J Coleman, J D White, B Lane, A Rosen, J Tinklenberg, C M Belden, A Atri, B M Spann, K A Clark, E Zamrini, M Sabbagh, R Killiany, R Stern, J Mez, N Kowall, A E Budson, T O Obisesan, O E Ntekim, S Wolday, J I Khan, E Nwulia, S Nadarajah, A Lerner, P Ogrocki, C Tatsuoka, P Fatica, E Fletcher, P Maillard, J Olichney, C DeCarli, O Carmichael, V Bates, H Capote, M Rainka, M Borrie, T Lee, R Bartha, S Johnson, S Asthana, C M Carlson, A Perrin, A Burke, D W Scharre, M Kataki, R Tarawneh, B Kelley, D Hart, E A Zimmerman, D Celmins, D D Miller, L L B Ponto, K E Smith, H Koleva, H Shim, K W Nam, S K Schultz, J D Williamson, S Craft, J Cleveland, M Yang, K M Sink, B R Ott, J D Drake, G Tremont, L A Daiello, M Sabbagh, A Ritter, C Bernick, D Munic, A Mintz, A O'Connell, J Mintzer, A Williams, J Masdeu, J Shi, A Garcia, M Sabbagh, P Newhouse, S Potkin, S Salloway, P Malloy, S Correia, S Kittur, G D Perlson, K Blank, K Anderson, L A Flashman, M Seltzer, M L Hynes, R B Santulli, N Relkin, G Chiang, A Lee, M Lin, L Ravdin

Affiliations

¹ Sanders-Brown Center on Aging, University of Kentucky, Lexington, KY, USA.
² Department of Biology, Brigham Young University, Provo, UT, USA.
³ Division of Biomedical Informatics, Department of Internal Medicine, University of Kentucky, Lexington, KY, USA.
⁴ Department of Neuroscience, University of Kentucky, Lexington, KY, USA.
⁵ Department of Pathology and Laboratory Medicine, University of Kentucky, Lexington, KY, USA.
⁶ Department of Biology, Brigham Young University, Provo, UT, USA. kauwe@byu.edu.

^# Contributed equally.

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.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Research Support, U.S. Gov't, Non-P.H.S.

MeSH terms

Genetic Predisposition to Disease
Genome-Wide Association Study*
Humans
Knowledge Bases
Multifactorial Inheritance*
Polymorphism, Single Nucleotide
Risk Factors

Abstract

Publication types

MeSH terms

Grants and funding