Heritabilities of radiologic osteoarthritis in peripheral joints and of disc degeneration of the spine

Abstract

Objective. To estimate the genetic influence on the occurrence of radiologic osteoarthritis (ROA) in the knees, hips, and hands and disc degeneration of the spine in the general population. Methods. A random sample of 1,583 individuals was drawn to estimate the prevalence of ROA and disc degeneration in the general population. Of 118 pro-bands with multiple affected joint sites who were derived from this sample, we were able to recruit 257 siblings. The variance of ROA and disc degeneration within sibling pairs was compared with the variance between sibling pairs. Heritability estimates for ROA in the knees, hips, and hands and for disc degeneration of the spine were calculated. OA was defined according to radiologic criteria, using the Kellgren/Lawrence grading system. Results. We observed that hand ROA and disc degeneration of the spine were statistically significantly more frequent in siblings than in the random sample, whereas the prevalence of knee and of hip ROA was similar and lower, respectively. Heritability estimates for hand ROA and disc degeneration were statistically significant, P 0.56 (95% confidence interval [95% CI] 0.34-0.76) and P 0.75 (95% CI 0.30-1.00), respectively. For knee and hip ROA, no evidence of a genetic effect in the general population was found. Finally, the heritability estimate for a score that summed the number of joints affected in the knees, hips, hands, and spine was 0.78 (95% CI 0.52-0.98). All heritability estimates were adjusted for age, sex, body mass index, and bone mineral density. Conclusion. The present study shows that in the general population, there is a strong genetic effect for hand ROA and disc degeneration of the spine. The findings on the total number of joints affected at multiple sites suggest genetic susceptibility to generalized OA. A genetic effect on osteoarthritis (OA) was initially recognized in 1941 by Stecher, who showed that Heberden's nodes of the fingers were more common in sisters of affected subjects than in the general population (1). In 1963, Kellgren et al (2), in a study of subjects derived from an outpatient clinic, reported that first-degree relatives of subjects with generalized radiologic OA (ROA) were twice as likely to have ROA than was expected in the general population. In 1996, Spector et al (3) measured ROA in the hands and knees of female twins and suggested that genetic factors might explain up to 65% of the variability in ROA of the hand and knee. This familial aggregation of hand and knee ROA was confirmed recently in 2 population-based studies (4,5). Furthermore, Felson et al (4), in a segregation analysis, found evidence of effects of a major recessive gene with a residual multifactorial component. With the exception of the study by Kellgren et al (2), previous studies concerning the role of genetic factors in the occurrence of ROA were limited to OA of the hands and knees (3-5). The contribution of genetic factors to other common forms of OA, including hip

Mutation analysis of candidate genes within the 2q33.3 linkage area for familial early-onset generalised osteoarthritis

“…In a random sample of 809 unrelated subjects (the Rotterdam sample), ages 55 -65 years, radiographs were scored for the presence of ROA in two knees, two hips, 19 36 hand joints and three levels of the thoracocolumbar spine. 19,20 All radiographs were scored according to the Kellgren/Lawrence grading system (grades 0 -4) 17 by two independent readers, blinded to all other data of the participant. Definite ROA at a particular joint site was defined as a Kellgren/Lawrence score of two or more.…”

Strong linkage on 2q33.3 to familial early-onset generalized osteoarthritis and a consideration of two positional candidate genes

“…In epidemiological studies, the term is used to describe subjects with 2 -3 radiographically affected sites, which may occur relatively frequent at ages above 55 years when considering, for example, hand and spine. 2 In contrast, the diagnosis of FOA in our families reflect patients with early onset symptomatic polyarticular disease, affecting typical as well as atypical sites and occurs in an autosomal-dominant inheritance patterns. 13 Such a specific phenotype is rare, however, emerged after radiographic and physical examination as homogeneous among our family members.…”

“…In a random sample of 1369 unrelated subjects (the Rotterdam sample), aged 55 -70 years, radiographs were scored for the presence of ROA in two knees, two hips, 16 36 hand joints and three levels of the thoracocolumbar spine. 2 All radiographs were scored according to the Kellgren's criteria 14 by two independent readers, blinded to all other data of the participant. Definite ROA was defined as a Kellgren's score of Z2.…”

“…Genetic factors play an important role in the etiology of the disease, especially for OA at the hand or hip, for disc degeneration (DD) and for OA at multiple sites. 1,2 Segregation analysis of families with generalized OA indicated the presence of a major recessive OA gene with a residual multifactorial component. 3 Together, it has become clear that different definitions of OA must be considered as distinct entities and may be caused by different (sets of) genes.…”

Lower prevalence of hand osteoarthritis among Chinese subjects in Beijing compared with white subjects in the United States: The Beijing Osteoarthritis Study

“…Several studies have shown that both hand OA and hip OA are highly heritable (4-6), more so than knee OA (7). If genetic predisposition accounts for the low prevalence of hip OA in the Chinese, we might expect that the Chinese would also have a lower prevalence of hand OA than that among whites.…”