Familial aggregation of osteoarthritis: Data from the Baltimore longitudinal study on aging

Hirsch, Rosemarie; Lethbridge-Çejku, Margaret; Hanson, Robert L.; Scott, William W.; Reichle, R; Plato, Chris C.; Tobin, Jordan D.; Hochberg, Marc C.

doi:10.1002/1529-0131(199807)41:7<1227::aid-art13>3.0.co;2-n

Cited by 110 publications

(63 citation statements)

References 9 publications

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“…In Table 3, the findings of the present study are compared with the findings of the 3 previous studies on the heritability of OA, including a twin study and 2 population-based studies (3)(4)(5). For the sake of comparability, we also calculated sib-sib correlations (Table 3).…”

Section: Discussionmentioning

confidence: 93%

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

Bijkerk¹,

Houwing-Duistermaat²,

Valkenburg³

et al. 1999

Arthritis & Rheumatism

126

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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

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Section: Discussionmentioning

confidence: 93%

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

Bijkerk¹,

Houwing-Duistermaat²,

Valkenburg³

et al. 1999

Arthritis & Rheumatism

126

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“…It has been demonstrated that genetic factors also play an important role in late-onset OA. Familial aggregation of OA (especially hand, knee, and hip OA) was observed in population-based studies (1)(2)(3)(4). Candidate genes that may exert this genetic influence have been investigated by means of population-based association studies and genetic linkage studies in OA families.…”

Section: Discussionmentioning

confidence: 99%

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

Meulenbelt

Seymour

Nieuwland

et al. 2004

Arthritis & Rheumatism

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Objective. To study the role of the interleukin-1␤ gene (IL1B) and the IL-1 receptor antagonist gene (IL1RN) in relation to the occurrence of radiographic osteoarthritis (ROA) in the hip, knee, and hand and disc degeneration of the spine.Methods. The study population consisted of a random sample of 886 subjects (ages 55-65 years) from a population-based cohort (the Rotterdam study). Two polymorphisms within IL1B (3953C>T and ؊511C>T) and one within IL1RN (the variable-number tandem repeat [VNTR]) were analyzed and used in an association study of the occurrence of ROA. Haplotyping and simultaneous logistic regression analysis were performed to investigate whether the associations observed were independent.Results. Associations with a predisposition for hip ROA were observed for heterozygous and homozygous carriers of the rare IL1B allele ؊511T (crude odds ratio [OR] 1.8, 95% confidence interval [95% CI] 1.0-3.4 and OR 2.9, 95% CI 1.4-6.3, respectively) and of the IL1RN VNTR allele 2 (crude OR 2.0, 95% CI 1.1-3.4 and OR 3.3, 95% CI 1.4-7.8, respectively). An additive effect was observed for carriers of risk alleles of both polymorphisms, with a significant linear-by-linear association (P ‫؍‬ 0.00022). Conclusion.Our findings suggest that the IL-1 gene cluster polymorphisms may play a significant role in the pathogenesis of OA of the hip.Osteoarthritis (OA) is a joint disease characterized by degeneration of articular cartilage and remodeling of the subchondral bone with sclerosis. It has been demonstrated that genetic factors also play an important role in late-onset OA. Familial aggregation of OA (especially hand, knee, and hip OA) was observed in population-based studies (1-4). Candidate genes that may exert this genetic influence have been investigated by means of population-based association studies and genetic linkage studies in OA families. A large number of association studies using various definitions of OA have been performed, mainly investigating genes encoding structural proteins of the extracellular matrix of cartilage (e.g., COL2A1, CRTM, and AGN) or genes playing a role in the regulation of bone density and mass (e.g., VDR, IGF1, and ER), and have shown both positive and negative results for each of the genes (for review, see ref. 5). These differences in study results may indicate either false-positive or false-negative results, could be the result of differences in the OA phenotype investigated, or could be attributable to different linkage disequilibrium (LD) between the associated polymorphism and the causal mutation in various populations. Moreover, it is becoming increasingly clear that the genetic risk factors for OA at different joint sites may be distinct (6).Several groups of investigators have performed genome-wide screens of sibling pairs or nuclear families with OA and reported multiple chromosome areas (e.g., 2p24, 3p12, 4q32, 11q12, 4q27, Xp11.3, and 7p22) that show positive linkage to specific OA phenotypes, such as radiographic OA (ROA) in the distal interphalangeal (DIP) joints, s...

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“…For OA of the knee, no significant correlation was found (r = 0.33); however, as the authors themselves stated, this finding could be due to underestimating of the number of cases of knee OA. The results from this cohort demonstrate familial aggregation of OA and suggest that genes could play a more significant role in severity than in occurrence (Hirsch et al, 1998). This, however, does not exclude a role for environmental influences because the authors did not look for putative environmental factors, as frequently occurs in large-scale studies in which control or ascertainment of all variables is difficult.…”

Section: Population-based Family Studiesmentioning

confidence: 79%

The Genetics of Osteoarthritis

Miranda‐Duarte¹

2012

Principles of Osteoarthritis- Its Definition, Character, Derivation and Modality-Related Recognition

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Familial aggregation of osteoarthritis: Data from the Baltimore longitudinal study on aging

Cited by 110 publications

References 9 publications

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

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

Association of the interleukin‐1 gene cluster with radiographic signs of osteoarthritis of the hip

The Genetics of Osteoarthritis

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