Table 2 Summary of gene–osteoarthritis (OA)/spinal degenerative disease (SDD) association studies
Gene*Joints affected†References
HipKneeHip/kneeHandSpineMultipleAny
ACE0/1Hong et al8
ACVR10/1Loughlin et al9
ADAM121/2Valdes et al 10 11
ADAMTS31/1Kawahara et al12
AEBP10/1Valdes et al10
AGC11/10/23/31/2Kawaguchi et al,13 Kirk et al,14 Horton et al,15 Noponen-Hietala et al16 and Kamarainen et al17
AR1/1Fytili et al18
ASPN2/33/51/10/1Kizawa et al,19 Mustafa et al,20 Jiang et al,21 Kaliakatsos et al22 and Rodriguez-Lopez et al23
ATF20/1Loughlin et al9
BGN0/1Valdes et al10
BMP21/2Valdes et al10 11
BMP51/1Southam et al24
BMPR1A0/1Valdes et al10
CALM11/2Mototani et al,25 and Loughlin et al26
CD361/2Valdes et al10 11
CD550/1Valdes et al10
CILP1/21/1Valdes et al10 11 and Seki et al 27
CLEC3B1/2Valdes et al10 11
COL1A11/30/10/11/1Aerssens et al,28 Loughlin et al,29 Lain et al30 and Pluijm et al31
COL2A10/41/30/10/10/11/3Aerssens et al,28 Granchi et al,32 Ikeda et al,33 Jakkula et al,34 Meulenbelt et al,35 Priestley et al,36 Vikkula et al,37 Uitterlinden et al38 and Solovieva et al 39
COL9A11/30/20/10/1Ikeda et al,33 Jakkula et al,34 Alizadeh et al40 and Jim et al41
COL9A20/20/20/12/4Ikeda et al,33 Jakkula et al,34 Jim et al,41 Kales et al,42 Seki et al43 and Annunen et al44
COL9A30/21/21/12/4Ikeda et al,33 Jakkula et al,34 Solovieva et al,39 45 Jim et al,41 and Kales et al42
COL10A10/20/20/1Ikeda et al33 and Jakkula et al34
COL11A10/20/20/1Ikeda et al33 and Jakkula et al34
COL11A20/20/20/12/2Noponen-Hietala et al,16 Ikeda et al,33 Jakkula et al34 and Solovieva et al39
COMP0/10/2Valdes et al10 and Mabuchi et al46
CTSL0/1Valdes et al10
ENPP11/1Suk et al47
ESR10/12/60/10/21/1Valdes et al,10 11 Fytili et al,18 Loughlin et al,29 Bergink et al,48 Jin et al,49 Kawagichi et al,50 Ushiyama et al51 and Koshizuka et al52
ESR21/1Fytili et al18
FAP0/1Loughlin et al9
FRZB3/52/2Loughlin et al,9 Min et al,53 Lane et al54 and Lories et al 55
HAPLN10/10/1Meulenbelt et al56
HFE0/10/12/2‡Ross et al,57 Carroll58 and Loughlin et al59
HLA-A0/1Wakitani et al60
HLA-B0/1Wakitani et al60
HLA-C1/1Wakitani et al60
HLA-DQA10/1Wakitani et al60
HLA-DQB10/1Wakitani et al60
HLA-DRB11/10/10/11/1Wakitani et al,60 Moos et al61 and Rovetta et al62
HLA-DRB30/1Wakitani et al60
IBSP0/1Valdes et al10
IGF11/11/11/11/10/11/1Meulenbelt et al63
IGF21/1Zhai et al64
IGFBP70/1Kawahara et al12
IL1A0/12/20/11/1Solovieva et al,65 Stern et al,66 Loughlin et al67 and Smith et al68
IL1B1/21/21/11/11/2Koshizuka et al,52 Solovieva et al,65 Stern et al,66 Loughlin et al,67 Smith et al,68 Moos et al69 and Meulenbelt et al70
IL1R10/1Smith et al68
IL1RN1/22/21/10/11/1Solovieva et al,65 Stern et al,66 Loughlin et al,67 Smith et al,68 Moos et al69 and Meulenbelt et al70
IL4R1/1Forster et al71
IL61/10/1Moos et al69 and Pola et al72
IL80/1Kawahara et al12
IL101/10/1Riyazi et al73 and Fytili et al74
IL17A0/1Southam et al75
IL17F0/1Southam et al75
ITGA40/1Loughlin et al9
ITGA50/1Loughlin et al9
ITGA61/1Loughlin et al9
KL1/1Ogata et al76
LRCH11/1Spector et al77
LRP51/1Smith et al78
MATN11/20/20/1Meulenbelt et al,56 Strusberg et al79 and Loughlin et al80
MATN30/10/10/11/1Min et al81
Mit. seq§0/1Chang et al82
MMP30/11/2Valdes et al,10 Noponen-Hietala et al16 and Takahashi et al83
MXRA50/1Valdes et al10
NCOR21/2Valdes et al10 11
OGN0/1Valdes et al10
PAPSS20/1Ikeda et al84
PPARG0/1Cheng et al85
PTGS22/2Valdes et al10 11
PTH0/1Koshizuka et al52
SERPINA10/1Sakkas et al86
SERPINA31/21/1Valdes et al10 11 and Sakkas et al86
SLC26A21/1Ikeda et al84
SOD30/1Valdes et al10
TGFB11/1Yamada et al87
TIMP10/1Valdes et al10
TNF0/1Moos et al69
TNFAIP61/10/2Loughlin et al9 and Valdes et al10 11
TNFRSF11B0/2Valdes et al10 11
VDR0/42/70/11/45/80/1Valdes et al,10 11 Noponen-Hietala et al,16 Aerssens et al,28 Loughlin et al,29 Granchi et al,32 Kawaguchi et al,50 Koshizuka et al,52 Huang et al,88 Jones et al,89 Jordan et al,90 Keen et al,91 Uitterlinden et al,92 Videman et al,93 Cheung et al,94 Solovieva et al95 and Baldwin et al96
  • The total numbers of significant associations for each joint group are expressed in relation to the total number of studies per gene/joint combination (eg, AGC1, Spine  = 1/2: one significant association reported from two separate studies).

  • *See table 1.

  • †Symbols as approved by the Human Genome organisation (HUGO; see http://ash.gene.ucl.ac.uk/nomenclature/). Approved gene names are as follows: ACE, angiotensin I converting enzyme; ACVR1, activin A receptor, type I; ADAM12, ADAM metallopeptidase domain 12; ADAMTS3, ADAM metallopeptidase with thrombospondin type 1 motif, 3; AEBP1, AE binding protein 1; AGC1, aggrecan 1; AR, androgen receptor; ASPN, asporin; ATF2, activating transcription factor 2; BGN, biglycan; BMP2, bone morphogenetic protein 2; BMP5, bone morphogenetic protein 5; BMPR1A, bone morphogenetic protein receptor, type IA; CALM1, calmodulin 1; CD36, CD36 molecule; CD55, CD55 molecule; CILP, cartilage intermediate layer protein, nucleotide pyrophosphohydrolase; CLEC3B, C-type lectin domain family 3, member B; COL1A1, collagen, type I, alpha 1; COL2A1, collagen, type II, alpha 1; COL9A1, collagen, type IX, alpha 1; COL9A2, collagen, type IX, alpha 2; COL9A3, collagen, type IX, alpha 3; COL10A1, collagen, type X, alpha 1; COL11A1, collagen, type XI, alpha 1; COL11A2, collagen, type XI, alpha 2; COMP, cartilage oligomeric matrix protein; CTSL, cathepsin L; ENPP1, ectonucleotide pyrophosphatase/phosphodiesterase 1; ESR1, oestrogen receptor 1; ESR2, oestrogen receptor 2; FAP, fibroblast activation protein, alpha; FRZB, frizzled-related protein; HAPLN1, hyaluronan and proteoglycan link protein 1; HFE, haemochromatosis; HLA-A, major histocompatability complex (MHC), class I, A; HLA-B, MHC, class I, B; HLA-C, MHC, class I, C; HLA-DQA1, MHC, class II, DQ alpha 1; HLA-DQB1, MHC, class II, DQ beta 1; HLA-DRB1, MHC, class II, DR beta 1; HLA-DRB3, MHC, class II, DR beta 3; IBSP, integrin-binding sialoprotein; IGF1, insulin-like growth factor 1; IGF2, insulin-like growth factor 2; IGFBP7, insulin-like growth factor binding protein 7; IL1A, interleukin 1, alpha; IL1B, interleukin 1, beta; IL1R1, interleukin 1 receptor, type I; IL1RN, interleukin 1 receptor antagonist; IL4R, interleukin 4 receptor; IL6, interleukin 6; IL8, interleukin 8; IL10, interleukin 10; IL17A, interleukin 17A; IL17F, interleukin 17F; ITGA4, integrin, alpha 4; ITGA5, integrin, alpha 5; ITGA6, integrin, alpha 6; KL, klotho; LRCH1, leucine-rich repeats and calponin homology (CH) domain-containing 1; LRP5, low density lipoprotein receptor-related protein 5; MATN1, matrilin 1, cartilage matrix protein; MATN3, matrilin 3; MMP3, matrix metallopeptidase 3; MXRA5, matrix-remodelling associated 5; NCOR2,nuclear receptor co-repressor 2; OGN, osteoglycin; PAPSS2, 3′-phosphoadenosine 5′-phosphosulfate synthase 2; PPARG, peroxisome proliferator-activated receptor gamma; PTGS2, prostaglandin-endoperoxide synthase 2; PTH, parathyroid hormone; SERPINA1, serpin peptidase inhibitor, clade A, member 1; SERPINA3, serpin peptidase inhibitor, clade A, member 3; SLC26A2, solute carrier family 26, member 2; SOD3, superoxide dismutase 3, extracellular; TGFB1, transforming growth factor, beta 1; TIMP1, TIMP metallopeptidase inhibitor 1; TNF, tumour necrosis factor; TNFAIP6, tumour necrosis factor, alpha-induced protein 6; TNFRSF11B, tumour necrosis factor receptor superfamily, member 11b; VDR, vitamin D receptor. ‡Association also reported for the ankle for this gene,97 although not replicated in Carroll.58

  • § mtDNA deletion of 4977 base pairs.