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Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

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Autor
Boer C.G., Hatzikotoulas K., Southam L., Stefánsdóttir L., Zhang Y., Coutinho de Almeida R., Wu T.T., Zheng J., Hartley A., Teder-Laving M., Skogholt A.H., Terao C., Zengini E., Alexiadis G., Barysenka A., Bjornsdottir G., Gabrielsen M.E., Gilly A., Ingvarsson T., Johnsen M.B., Jonsson H., Kloppenburg M., Luetge A., Lund S.H., Mägi R., Mangino M., Nelissen R.R.G.H.H., Shivakumar M., Steinberg J., Takuwa H., Thomas L.F., Tuerlings M., Loughlin J., Arden N., Birrell F., Carr A., Deloukas P., Doherty M., McCaskie A.W., Ollier W.E.R., Rai A., Ralston S.H., Spector T.D., Wallis G.A., Martinsen A.E., Willer C., Fors E.A., Mundal I., Hagen K., Nilsen K.B., Lie M.U., Børte S., Brumpton B., Nielsen J.B., Fritsche L.G., Zhou W., Heuch I., Storheim K., Tyrpenou E., Koukakis A., Chytas D., Evangelopoulos D.S., Efstathios C., Pneumaticos S., Nikolaou V.S., Malizos K., Anastasopoulou L., Abecasis G., Baras A., Cantor M., Coppola G., Deubler A., Economides A., Lotta L.A., Overton J.D., Reid J.G., Shuldiner A., Karalis K., Siminovitch K., Beechert C., Forsythe C., Fuller E.D., Gu Z., Lattari M., Lopez A., Schleicher T.D., Padilla M.S., Widom L., Wolf S.E., Pradhan M., Manoochehri K., Bai X., Balasubramanian S., Boutkov B., Eom G., Habegger L., Hawes A., Krasheninina O., Lanche R., Mansfield A.J., Maxwell E.K., Nafde M., O'Keeffe S., Orelus M., Panea R., Polanco T., Rasool A., Salerno W., Staples J.C., Li D., Sharma D., Banerjee I., Bovijn J., Locke A., Verweij N., Haas M., Hindy G., De T., Akbari P., Sosina O., Ferreira M.A.R., Jones M.B., Mighty J., LeBlanc M.G., Mitnaul L.J., Babis G.C., Cheung J.P.Y., Kang J.H., Kraft P., Lietman S.A., Samartzis D., Slagboom P.E., Stefansson K., Thorsteinsdottir U., Tobias J.H., Uitterlinden A.G., Winsvold B., Zwart J.-A., Davey Smith G., Sham P.C., Thorleifsson G., Gaunt T.R., Morris A.P., Valdes A.M., Tsezou A., Cheah K.S.E., Ikegawa S., Hveem K., Esko T., Wilkinson J.M., Meulenbelt I., Lee M.T.M., van Meurs J.B.J., Styrkársdóttir U., Zeggini E., arcOGEN Consortium, HUNT All-In Pain, ARGO Consortium, Regeneron Genetics Center
Fecha
2021
Language
en
DOI
Materia
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Resumen
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. © 2021 The Authors
URI
http://hdl.handle.net/11615/71733
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