<p class="first" id="d12282039e378">Osteoarthritis has a highly negative impact on
quality of life because of the associated
pain and loss of joint function. Here we describe the largest meta-analysis so far
of osteoarthritis of the hip and the knee in samples from Iceland and the UK Biobank
(including 17,151 hip osteoarthritis patients, 23,877 knee osteoarthritis patients,
and more than 562,000 controls). We found 23 independent associations at 22 loci in
the additive meta-analyses, of which 16 of the loci were novel: 12 for hip and 4 for
knee osteoarthritis. Two associations are between rare or low-frequency missense variants
and hip osteoarthritis, affecting the genes SMO (rs143083812, frequency 0.11%, odds
ratio (OR) = 2.8, P = 7.9 × 10-12, p.Arg173Cys) and IL11 (rs4252548, frequency 2.08%,
OR = 1.30, P = 2.1 × 10-11, p.Arg112His). A common missense variant in the COL11A1
gene also associates with hip osteoarthritis (rs3753841, frequency 61%, P = 5.2 ×
10-10, OR = 1.08, p.Pro1284Leu). In addition, using a recessive model, we confirm
an association between hip osteoarthritis and a variant of CHADL1 (rs117018441, P
= 1.8 × 10-25, OR = 5.9). Furthermore, we observe a complex relationship between height
and risk of osteoarthritis.
</p>