When we incorporated missense (MIS) in addition to LOF variants (LOF + MIS) in the burden tests, we identified ADAMTSL3, VIT, IL11, THBS3, ADAMTS6, SPRY2 and COLGALT2 associated with osteoarthritis, of which association of ADAMTSL3 with hip osteoarthritis and IL11 with total hip replacement are genome-wide significant. This evidence concerns the gene SPRY2 and osteoarthritis.