Genetic architecture of knee radiographic joint space in healthy young adults.
Evidence of a significant genetic component to the age-related degenerative joint disease osteoarthritis has been established, but the nature of genetic influences on normal joint morphology in healthy individuals remains unclear. Following up on our previous findings on the influence of body habitus on phenotypic variation in knee joint space [Duren et al., Human Biology 78:353-364 (2006)], the objective of the current study was to estimate the heritability of radiographic joint space in the knees of healthy young adults from a community-based sample of families. A sample of 253 subjects (mean age = 18.02 years) from 87 randomly ascertained nuclear and extended families was examined. Joint width (JW) and minimum joint space in the medial (MJS) and lateral (LJS) knee compartments were measured. A maximum-likelihood variance components method was used to estimate the heritability of MJS, LJS, and JW. Covariate effects of age, sex, age-by-sex interactions, stature, weight, and BMI were simultaneously estimated. Genetic correlation analyses were then conducted to examine relationships between trait pairs. MJS, LJS, and JW were each significantly heritable (p < 0.001), with heritabilities of 0.52, 0.53, and 0.63, respectively. The genetic correlation between MJS and LJS was not significantly different from 1. Genetic correlations between each joint space measure and JW were not significantly different from 0. This study demonstrates a significant genetic component to radiographic knee joint space during young adulthood in healthy subjects. This suggests that there are specific but as yet unidentified genes that influence the morphology of healthy articular cartilage, the target tissue of osteoarthritis. Genetic correlation analyses indicate complete pleiotropy between MJS and LJS but genetic independence of joint space and JW.
Duren
Dana L
DL
Department of Community Health, Lifespan Health Research Center, Boonshoft School of Medicine, Wright State University, 3171 Research Boulevard, Dayton, OH 45420-4014, USA.
Sherwood
Richard J
RJ
Czerwinski
Stefan A
SA
Chumlea
William Cameron
WC
Lee
Miryoung
M
Demerath
Ellen W
EW
Sun
Shumei S
SS
Siervogel
Roger M
RM
Towne
Bradford
B
D000293:Adolescent; D000328:Adult; D005190:Family; D005260:Female; D006801:Humans; D007719:Knee Joint / Q000033:anatomy & histology / Q000000981:diagnostic imaging*; D008137:Longitudinal Studies; D008297:Male; D020370:Osteoarthritis, Knee / Q000235:genetics*; D011859:Radiography