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

Author

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, 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, Smith GD, Sham PC, Thorleifsson G, Gaunt TR, Morris AP, Valdes AM, Tsezou A, Cheah KSE, Ikegawa S, Hveem K, Esko T, Wilkinson JM, Meulenbelt I, Michael Lee MT, van Meurs JBJ, Styrkársdóttir U, and Zeggini E

Published
2021
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2. Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations.

Author

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, 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, and Zeggini E

Subjects
Female, Genome-Wide Association Study, Humans, Osteoarthritis drug therapy, Phenotype, Polymorphism, Single Nucleotide genetics, Risk Factors, Sex Characteristics, Signal Transduction genetics, Genetic Predisposition to Disease, Genetics, Population, Osteoarthritis genetics
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., Competing Interests: Declaration of interests T.R.G. and J.Z. receive research funding from GlaxoSmithKline. T.R.G. receives research funding from Biogen. U.S., K.S., L. Stefánsdóttir, G.B., S.H.L., U.T., and G. T. are employed by deCODE genetics/Amgen Inc. A.M.V. is a consultant for Zoe Global Ltd. All other authors report no competing interests. All Regeneron Genetics Center banner authors are current employees and/or stockholders of Regeneron Pharmaceuticals., (Copyright © 2021 The Authors. Published by Elsevier Inc. All rights reserved.)

Published
2021
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