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Boer, Cindy G.; Hatzikotoulas, Konstantinos; Southam, Lorraine; Zhang, Yanfei; Coutinho de Almeida, Rodrigo; Wu, Tian T.; Zheng, Jie; Hartley, April; Teder-Laving, Maris; Terao, Chikashi; Zengini, Eleni; Alexiadis, George; Bjornsdottir, Gyda; Gilly, Arthur; Ingvarsson, Thorvaldur; Luetge, Almut; Lund, Sigrun H.; Mangino, Massimo; Takuwa, Hiroshi; Thomas, Laurent F.; Loughlin, John; Arden, Nigel; Doherty, Michael; Ollier, William E.R.; Spector, Tim D.; Wallis, Gillian A.; Martinsen, Amy E.; Fors, Egil Andreas; Hagen, Knut; Nilsen, Kristian Bernhard; Lie, Marie Udnesseter; Børte, Sigrid; Brumpton, Ben; Fritsche, Lars G.; Zhou, Wei; Heuch, Ingrid; Storheim, Kjersti; Tyrpenou, Evangelos; Koukakis, Athanasios; Efstathios, Chronopoulos; Nikolaou, Vasileios S.; Malizos, Konstantinos; Anastasopoulou, Lydia; Abecasis, Goncalo; Baras, Aris; Cantor, Michael; Coppola, Giovanni; Lotta, Luca A.; Shuldiner, Alan; Karalis, Katia; Siminovitch, Katherine; Beechert, Christina; Forsythe, Caitlin; Fuller, Erin D.; Gu, Zhenhua; Lattari, Michael; Padilla, Maria Sotiropoulos; Widom, Louis; Wolf, Sarah E.; Pradhan, Manasi; Manoochehri, Kia; Bai, Xiaodong; Balasubramanian, Suganthi; Boutkov, Boris; Eom, Gisu; Habegger, Lukas; Hawes, Alicia; Maxwell, Evan K.; Orelus, Max; Panea, Razvan; Polanco, Tommy; Salerno, William; Staples, Jeffrey C.; Li, Dadong; Sharma, Deepika; Banerjee, Ilanjana; Locke, Adam; Haas, Mary; Akbari, Parsa; Ferreira, Manuel A.R.; Jones, Marcus B.; Mitnaul, Lyndon J.; Babis, George C.; Cheung, Jason Pui Yin; Kang, Jae Hee; Lietman, Steven A.; Samartzis, Dino; Stefansson, Kari; Uitterlinden, André G.; Davey Smith, George; Valdes, Ana M.; Tsezou, Aspasia; Cheah, Kathryn S.E.; Hveem, Kristian; Wilkinson, J. Mark; Meulenbelt, Ingrid; Lee, Ming Ta Michael; van Meurs, Joyce B.J.; Styrkársdóttir, Unnur; Zeggini, Eleftheria
Cell, 09/2021, Letnik: 184, Številka: 18Journal Article
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. Display omitted •A multicohort study identifies 52 previously unknown osteoarthritis genetic risk variants•Similarities and differences in osteoarthritis genetic risk depend on joint sites•Osteoarthritis genetic components are associated with pain-related phenotypes•High-confidence effector genes highlight potential targets for drug intervention A multicohort genome-wide association meta-analysis of osteoarthritis highlights the impact of joint site types on the features of genetic risk variants and the link between osteoarthritis genetics and pain-related phenotypes, pointing toward potential targets for therapeutic intervention.
