Table 2

Osteoarthritis risk-associated variants in enhancer regions of Hi-C identified enhancer-promoter loops

Lead variant (rsID)rs2276749rs8112559rs143083812rs12908498rs10405617rs10062749rs1321917
PhenotypeTHRHand OA
Finger OA
THR/Hip OAHip OA/THR/TJR
Knee-Hip OA/All OA
All OA/Knee OAHand OA/Thumb OA
Knee OA
THR/Hip OA/TJR
Variant position3:1160199119:458871977:12920356915:6707415019:106422925:1424255239:116562650
Credible set variantsrs2276749
rs6799718
rs8112559rs143083812rs1498506
rs1498507
rs10984rs28538668
rs6861056
rs1895062
Annotated effector geneVGLL4APOE3-SMAD3ILF3
SMARCA4
NR3C1-
Putative effector gene----SLC44A2*SPRY4PAPPA
Methylation and gene targets (QTLs)---cg09501821
eQTL (SMAD3)
cg01654627, cg17710535
eQTL (SLC44A2)
cg19514721cg08189448
Transcription factor affected-IRF, StatHic1, ATF3, ATF6
E2F, HEY1, Pax-4
AP-1, ATF3, E2F
INSM1, Jundm2
Foxd1AP-1, GATA, Pou2
  • Risk-associated phenotypes and lead variants were identified in the study by Boer et al.3 Lead variants are defined as the most significantly associated SNV for each of the credible set variants, Credible set variants are variants residing in the 95% credible sets, with a posterior probability of causality >3%. Annotated effector genes were genes identified to be associated with the lead variant in the study by Boer et al. Putative effector genes were identified in this study. Methylation targets and its QTLs were identified in a study by Kreitmaier et al41 and gene targets and their eQTLs in a study by Steinberg et al.39 Transcription factors affected by the credible set variant were identified with HaploReg V.4.2.43 44

  • *Colocalisation has been previously observed in the study by Boer et al in Genotype-Tissue Expression data, here we add additional support for SLC44A2.

  • All OA, osteoarthritis at any joint site; eQTL, expression QTL; Finger OA, finger osteoarthritis; Hand OA, hand osteoarthritis; Hip OA, hip osteoarthritis; Knee-Hip OA, knee and/or hip osteoarthritis; Knee OA, knee osteoarthritis; QTL, quantitative trait loci; SNV, single nucleotide variant; THR, total hip replacement; TJR, total joint replacement.