The DOT1L rs12982744 polymorphism is associated with osteoarthritis of the hip with genome-wide statistical significance in males

Osteoarthritis (OA) of the hip is a major cause of pain, disability and use of healthcare resources.1 Although OA is multifactorial, it is known to have significant genetic contribution and a number of studies have attempted to dissect such contribution (see2 for review). The DOT1L gene encodes the DOT1-like histone H3 methyltransferaseis, a potentially dedicated enzyme for Wnt target gene activation in leukaemia recently shown to be associated with endochondral bone formation.3 A polymorphism (rs12982744) in DOT1L has been found to be strongly associated with minimum joint space width (minJSW) at the hip. This exact same single nucleotide polymorphism (SNP) was previously identified to be associated with increased height.4 ,5 The C allele associated with lower minJSW and lower height was associated with hip OA, although this association did not reach genome-wide significance (GWS) (OR 1.14, CI 1.06 to 1.22; p=1.5  ×  10−4).3 The GWS level of p<5×10−8 is the threshold at which genetic associations are considered credible.6 The aim of our study was to prove that common genetic variation in the DOT1L gene is important …