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Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

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Authors
Boer, Cindy G
Hatzikotoulas, Konstantinos
Southam, Lorraine
Stefánsdóttir, Lilja
Zhang, Yanfei
Coutinho de Almeida, Rodrigo
Wu, Tian T
Zheng, Jie
Hartley, April
Teder-Laving, Maris
Skogholt, Anne Heidi
Terao, Chikashi
Zengini, Eleni
Alexiadis, George
Barysenka, Andrei
Bjornsdottir, Gyda
Gabrielsen, Maiken E
Gilly, Arthur
Ingvarsson, Thorvaldur
Johnsen, Marianne B
Jonsson, Helgi
Kloppenburg, Margreet
Luetge, Almut
Lund, Sigrun H
Mägi, Reedik
Mangino, Massimo
Nelissen, Rob R G H H
Shivakumar, Manu
Steinberg, Julia
Takuwa, Hiroshi
Thomas, Laurent F
Tuerlings, Margo
Babis, George C
Cheung, Jason Pui Yin
Kang, Jae Hee
Kraft, Peter
Lietman, Steven A
Samartzis, Dino
Slagboom, P Eline
Stefansson, Kari
Thorsteinsdottir, Unnur
Tobias, Jonathan H
Uitterlinden, André G
Winsvold, Bendik
Zwart, John-Anker
Davey Smith, George
Sham, Pak Chung
Thorleifsson, Gudmar
Gaunt, Tom R
Morris, Andrew P
Valdes, Ana M
Tsezou, Aspasia
Cheah, Kathryn S E
Ikegawa, Shiro
Hveem, Kristian
Esko, Tõnu
Wilkinson, J Mark
Meulenbelt, Ingrid
Lee, Ming Ta Michael
van Meurs, Joyce B J
Styrkársdóttir, Unnur
Zeggini, Eleftheria
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Issue Date
2021-08-26

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Boer CG, Hatzikotoulas K, Southam L, Stefánsdóttir L, Zhang Y, Coutinho de Almeida R, Wu TT, Zheng J, Hartley A, Teder-Laving M, Skogholt AH, Terao C, Zengini E, Alexiadis G, Barysenka A, Bjornsdottir G, Gabrielsen ME, Gilly A, Ingvarsson T, Johnsen MB, Jonsson H, Kloppenburg M, Luetge A, Lund SH, Mägi R, Mangino M, Nelissen RRGHH, Shivakumar M, Steinberg J, Takuwa H, Thomas LF, Tuerlings M; arcOGEN Consortium; HUNT All-In Pain; ARGO Consortium; Regeneron Genetics Center, Babis GC, Cheung JPY, Kang JH, Kraft P, Lietman SA, Samartzis D, Slagboom PE, Stefansson K, Thorsteinsdottir U, Tobias JH, Uitterlinden AG, Winsvold B, Zwart JA, Davey Smith G, Sham PC, Thorleifsson G, Gaunt TR, Morris AP, Valdes AM, Tsezou A, Cheah KSE, Ikegawa S, Hveem K, Esko T, Wilkinson JM, Meulenbelt I, Lee MTM, van Meurs JBJ, Styrkársdóttir U, Zeggini E. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations. Cell. 2021 Sep 2;184(18):4784-4818.e17. doi: 10.1016/j.cell.2021.07.038.
Abstract
Osteoarthritis affects over 300 million people worldwide. Here, we conduct a genome-wide association study meta-analysis across 826,690 individuals (177,517 with osteoarthritis) and identify 100 independently associated risk variants across 11 osteoarthritis phenotypes, 52 of which have not been associated with the disease before. We report thumb and spine osteoarthritis risk variants and identify differences in genetic effects between weight-bearing and non-weight-bearing joints. We identify sex-specific and early age-at-onset osteoarthritis risk loci. We integrate functional genomics data from primary patient tissues (including articular cartilage, subchondral bone, and osteophytic cartilage) and identify high-confidence effector genes. We provide evidence for genetic correlation with phenotypes related to pain, the main disease symptom, and identify likely causal genes linked to neuronal processes. Our results provide insights into key molecular players in disease processes and highlight attractive drug targets to accelerate translation.
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To access publisher's full text version of this article, please click on the hyperlink in Additional Links field or click on the hyperlink at the top of the page marked Download
Additional Links
https://www.sciencedirect.com/science/article/pii/S0092867421009417?via%3Dihub
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8459317/
Rights
Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.
ae974a485f413a2113503eed53cd6c53
10.1016/j.cell.2021.07.038
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