Limitations of Human Genetic Studies on Osteoarthritis

Abstract

1 (control; mAF=15.2%) [10]. The mAF of the omitted KL=2 subgroup was 12.3%, confirming an inverse relationship between mAF of the SNP and KL scores. This clearly indicates that inclusion of the KL=2 subjects in the case group had caused a decrease in the detection power. In fact, this association was not reproduced by conventional Japanese and Chinese studies that include KL=2 in the case group [11]. Considering that prevalence of the KL=2 subgroup is shown to be fairly high in representative epidemiologic studies (17.3-41.3%; difference between KL ≥ 2 and KL ≥ 3 in Table 2), removal of this subgroup may inevitably cause a decrease in the total sample size. Generally, a lack of objective and quantitative measure for the disease definition remains a fatal limitation of clinical OA studies. The ROAD study has recently established the fully automatic program KOACAD (knee OA computer-aided diagnosis) to quantify the major OA parameters (joint space, osteophyte, etc.) on plain radiographs [8]. We believe that the KOACAD system as well as magnetic resonance image systems [12] will serve as optimal measures for the definition of OA in the near future, just as bone mineral density does in osteoporosis.