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 probands 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.