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Boer, C.G.; Hatzikotoulas, K.; Southam, L.; Stefansdottir, L.; Zhang, Y.F.; Almeida, R.C. de; ... ; Regeneron Genetics Ctr (2021)

Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

Article / Letter to editor
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...Show moreOsteoarthritis 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.Show less
All authors
Boer, C.G.; Hatzikotoulas, K.; Southam, L.; Stefansdottir, L.; Zhang, Y.F.; Almeida, R.C. de; 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.; Magi, R.; Mangino, M.; Nelissen, R.R.G.H.H.; Shivakumar, M.; Steinberg, J.; Takuwa, H.; Thomas, L.F.; Tuerlings, M.; 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.; Smith, G.D.; 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.; Meurs, J.B.J. van; Styrkarsdottir, U.; Zeggini, E.; arcOGEN Consortium; HUNT All-In Pain; ARGO Consortium; Regeneron Genetics Ctr
Date
2021-09-02
Journal
Cell
Volume
184
Issue
18
Pages
4784 - 4818
DOI
doi:10.1016/j.cell.2021.07.038
Link
http://www.cell.com/article/S0092867421009417/pdf