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Article: Deciphering osteoarthritis genetics across 826,690 individuals from 9 populations

TitleDeciphering osteoarthritis genetics across 826,690 individuals from 9 populations
Authors
Boer, CGHatzikotoulas, KSoutham, LStefansdottir, LZhang, YFCoutinho de Almeida, RWU, TZheng, JHartley, ATeder-Laving, MSkogholt, AHDavey Smith, GSharma, DBanerjee, IBovijn, JLocke, AVerweij, NHaas, MHindy, GDe, TMagi, RCoppola, GAkbari, PSosina, OSham, PCBjornsdottir, GFerreira, MARJones, MBMighty, JLeBlanc, MGMitnaul, LJGabrielsen, MEEsko, TMangino, MGilly, AIngvarsson, TJohnsen, MBThorleifsson, GJonsson, HNelissen, RRGHHShivakumar, MSteinberg, JTakuwa, HWilkinson, JMGaunt, TRFors, EAThomas, LFTuerlings, MBabis, GCCheung, JPYKang, JHKraft, PLietman, SASamartzis, DMeulenbelt, ISlagboom, PEStefansson, KMundal, IMorris, APThorsteinsdottir, UTobias, JHUitterlinden, AGWinsvold, BZwart, JAValdes, AMLee, MTMTsezou, ACheah, KSEIkegawa, SHagen, KHveem, Kvan Meurs, JBJStyrkarsdottir, UZeggini, ELoughlin, JNilsen, KBTerao, CArden, NBirrell, FDeubler, ACarr, ADeloukas, PDoherty, MMcCaskie, AWOllier, WERRai, ARalston, SHForsythe, CLie, MUSpector, TDWallis, GAMartinsen, AEEconomides, AWiller, CBorte, SBrumpton, BNielsen, JBFritsche, LGFuller, EDLotta, LANafde, MZhou, WHeuch, IStorheim, KTyrpenou, EKoukakis, AChytas, DEvangelopoulos, DSEfstathios, CGu, ZHPneumaticos, SNikolaou, VSO'Keeffe, SOverton, JDMalizos, KAnastasopoulou, LAbecasis, GBaras, ACantor, MReid, JGLattari, MShuldiner, AKaralis, KSiminovitch, KOrelus, MBeechert, CLopez, ASchleicher, TDPadilla, MSWidom, LPanea, RKloppenburg, MWolf, SEPradhan, MZengini, EManoochehri, KBai, XDBalasubramanian, SBoutkov, BEom, GHabegger, LHawes, ALuetge, APolanco, TKrasheninina, OLanche, RMansfield, AJAlexiadis, GMaxwell, EKRasool, ASalerno, WStaples, JCLi, DDLund, SHBarysenka, A
Issue Date2021
PublisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell
Citation
Cell, 2021, v. 184 n. 18, p. 4784-4818.E17 How to Cite?
AbstractOsteoarthritis 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.
Persistent Identifierhttp://hdl.handle.net/10722/302345
ISSN
2023 Impact Factor: 45.5
2023 SCImago Journal Rankings: 24.342
PubMed Central ID
ISI Accession Number ID
Errata

 

DC FieldValueLanguage
dc.contributor.authorBoer, CG-
dc.contributor.authorHatzikotoulas, K-
dc.contributor.authorSoutham, L-
dc.contributor.authorStefansdottir, L-
dc.contributor.authorZhang, YF-
dc.contributor.authorCoutinho de Almeida, R-
dc.contributor.authorWU, T-
dc.contributor.authorZheng, J-
dc.contributor.authorHartley, A-
dc.contributor.authorTeder-Laving, M-
dc.contributor.authorSkogholt, AH-
dc.contributor.authorDavey Smith, G-
dc.contributor.authorSharma, D-
dc.contributor.authorBanerjee, I-
dc.contributor.authorBovijn, J-
dc.contributor.authorLocke, A-
dc.contributor.authorVerweij, N-
dc.contributor.authorHaas, M-
dc.contributor.authorHindy, G-
dc.contributor.authorDe, T-
dc.contributor.authorMagi, R-
dc.contributor.authorCoppola, G-
dc.contributor.authorAkbari, P-
dc.contributor.authorSosina, O-
dc.contributor.authorSham, PC-
dc.contributor.authorBjornsdottir, G-
dc.contributor.authorFerreira, MAR-
dc.contributor.authorJones, MB-
dc.contributor.authorMighty, J-
dc.contributor.authorLeBlanc, MG-
dc.contributor.authorMitnaul, LJ-
dc.contributor.authorGabrielsen, ME-
dc.contributor.authorEsko, T-
dc.contributor.authorMangino, M-
dc.contributor.authorGilly, A-
dc.contributor.authorIngvarsson, T-
dc.contributor.authorJohnsen, MB-
dc.contributor.authorThorleifsson, G-
dc.contributor.authorJonsson, H-
dc.contributor.authorNelissen, RRGHH-
dc.contributor.authorShivakumar, M-
dc.contributor.authorSteinberg, J-
dc.contributor.authorTakuwa, H-
dc.contributor.authorWilkinson, JM-
dc.contributor.authorGaunt, TR-
dc.contributor.authorFors, EA-
dc.contributor.authorThomas, LF-
dc.contributor.authorTuerlings, M-
dc.contributor.authorBabis, GC-
dc.contributor.authorCheung, JPY-
dc.contributor.authorKang, JH-
dc.contributor.authorKraft, P-
dc.contributor.authorLietman, SA-
dc.contributor.authorSamartzis, D-
dc.contributor.authorMeulenbelt, I-
dc.contributor.authorSlagboom, PE-
dc.contributor.authorStefansson, K-
dc.contributor.authorMundal, I-
dc.contributor.authorMorris, AP-
dc.contributor.authorThorsteinsdottir, U-
dc.contributor.authorTobias, JH-
dc.contributor.authorUitterlinden, AG-
dc.contributor.authorWinsvold, B-
dc.contributor.authorZwart, JA-
dc.contributor.authorValdes, AM-
dc.contributor.authorLee, MTM-
dc.contributor.authorTsezou, A-
dc.contributor.authorCheah, KSE-
dc.contributor.authorIkegawa, S-
dc.contributor.authorHagen, K-
dc.contributor.authorHveem, K-
dc.contributor.authorvan Meurs, JBJ-
dc.contributor.authorStyrkarsdottir, U-
dc.contributor.authorZeggini, E-
dc.contributor.authorLoughlin, J-
dc.contributor.authorNilsen, KB-
dc.contributor.authorTerao, C-
dc.contributor.authorArden, N-
dc.contributor.authorBirrell, F-
dc.contributor.authorDeubler, A-
dc.contributor.authorCarr, A-
dc.contributor.authorDeloukas, P-
dc.contributor.authorDoherty, M-
dc.contributor.authorMcCaskie, AW-
dc.contributor.authorOllier, WER-
dc.contributor.authorRai, A-
dc.contributor.authorRalston, SH-
dc.contributor.authorForsythe, C-
dc.contributor.authorLie, MU-
dc.contributor.authorSpector, TD-
dc.contributor.authorWallis, GA-
dc.contributor.authorMartinsen, AE-
dc.contributor.authorEconomides, A-
dc.contributor.authorWiller, C-
dc.contributor.authorBorte, S-
dc.contributor.authorBrumpton, B-
dc.contributor.authorNielsen, JB-
dc.contributor.authorFritsche, LG-
dc.contributor.authorFuller, ED-
dc.contributor.authorLotta, LA-
dc.contributor.authorNafde, M-
dc.contributor.authorZhou, W-
dc.contributor.authorHeuch, I-
dc.contributor.authorStorheim, K-
dc.contributor.authorTyrpenou, E-
dc.contributor.authorKoukakis, A-
dc.contributor.authorChytas, D-
dc.contributor.authorEvangelopoulos, DS-
dc.contributor.authorEfstathios, C-
dc.contributor.authorGu, ZH-
dc.contributor.authorPneumaticos, S-
dc.contributor.authorNikolaou, VS-
dc.contributor.authorO'Keeffe, S-
dc.contributor.authorOverton, JD-
dc.contributor.authorMalizos, K-
dc.contributor.authorAnastasopoulou, L-
dc.contributor.authorAbecasis, G-
dc.contributor.authorBaras, A-
dc.contributor.authorCantor, M-
dc.contributor.authorReid, JG-
dc.contributor.authorLattari, M-
dc.contributor.authorShuldiner, A-
dc.contributor.authorKaralis, K-
dc.contributor.authorSiminovitch, K-
dc.contributor.authorOrelus, M-
dc.contributor.authorBeechert, C-
dc.contributor.authorLopez, A-
dc.contributor.authorSchleicher, TD-
dc.contributor.authorPadilla, MS-
dc.contributor.authorWidom, L-
dc.contributor.authorPanea, R-
dc.contributor.authorKloppenburg, M-
dc.contributor.authorWolf, SE-
dc.contributor.authorPradhan, M-
dc.contributor.authorZengini, E-
dc.contributor.authorManoochehri, K-
dc.contributor.authorBai, XD-
dc.contributor.authorBalasubramanian, S-
dc.contributor.authorBoutkov, B-
dc.contributor.authorEom, G-
dc.contributor.authorHabegger, L-
dc.contributor.authorHawes, A-
dc.contributor.authorLuetge, A-
dc.contributor.authorPolanco, T-
dc.contributor.authorKrasheninina, O-
dc.contributor.authorLanche, R-
dc.contributor.authorMansfield, AJ-
dc.contributor.authorAlexiadis, G-
dc.contributor.authorMaxwell, EK-
dc.contributor.authorRasool, A-
dc.contributor.authorSalerno, W-
dc.contributor.authorStaples, JC-
dc.contributor.authorLi, DD-
dc.contributor.authorLund, SH-
dc.contributor.authorBarysenka, A-
dc.date.accessioned2021-09-06T03:30:57Z-
dc.date.available2021-09-06T03:30:57Z-
dc.date.issued2021-
dc.identifier.citationCell, 2021, v. 184 n. 18, p. 4784-4818.E17-
dc.identifier.issn0092-8674-
dc.identifier.urihttp://hdl.handle.net/10722/302345-
dc.description.abstractOsteoarthritis 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.-
dc.languageeng-
dc.publisherCell Press. The Journal's web site is located at http://www.elsevier.com/locate/cell-
dc.relation.ispartofCell-
dc.titleDeciphering osteoarthritis genetics across 826,690 individuals from 9 populations-
dc.typeArticle-
dc.identifier.emailCheung, JPY: cheungjp@hku.hk-
dc.identifier.emailSham, PC: pcsham@hku.hk-
dc.identifier.emailCheah, KSE: hrmbdkc@hku.hk-
dc.identifier.authorityCheung, JPY=rp01685-
dc.identifier.authoritySham, PC=rp00459-
dc.identifier.authorityCheah, KSE=rp00342-
dc.description.naturelink_to_OA_fulltext-
dc.identifier.doi10.1016/j.cell.2021.07.038-
dc.identifier.pmid34450027-
dc.identifier.pmcidPMC8459317-
dc.identifier.scopuseid_2-s2.0-85114044916-
dc.identifier.hkuros324753-
dc.identifier.hkuros332152-
dc.identifier.isiWOS:000692441200013-
dc.relation.erratumdoi:10.1016/j.cell.2021.11.003-

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