Relative role of genetic and environmental factors in disease expression: sib pair analysis in ankylosing spondylitis

Abstract

Forty-two sib pairs concordant for ankylosing spondylitis (mean disease duration 20.1 years) were assessed to define the relative role of genetic and environmental factors in determining age and calendar year of disease onset, systemic features, functional outcome and prognosis, and radiologic progression. Twenty-seven pairs were of the same sex (male/male n = 21, female/female n = 6). The correlation coefficient was not significant for age at onset (rs = 0.235), but was much higher for calendar year of onset (rs = 0.702, P less than 0.01). These data were confirmed by two-way analysis of variance: between sibs, the F probability was 0.07 for age at onset (41 degrees of freedom, F ratio 1.6) and was less than 0.001 for calendar year of onset (41 degrees of freedom, F ratio 5.45). Thus, it is suggested that environmental factors play the greater role in the timing of onset. Concordance for the presence or absence of uveitis was only 43%, again suggesting that genetic factors are less significant than the environment. Conversely, genetic factors are more important in influencing prognosis. A disability and pain index revealed that sibs had a closer score than expected by chance alone (P = 0.035); also, the correlation coefficient for blinded radiologic analysis (pelvic and lumbar views) was significant for pairs of sibs (rs = 0.859, P less than 0.01), but was not significant for random pairs of subjects (rs = -0.144). In contrast, within-sib pair and random subject-pair analyses of hip radiographs revealed rs = -0.111 and -0.033, respectively, neither of which was significant.(ABSTRACT TRUNCATED AT 250 WORDS)