Sibling recurrence risk ratio analysis of the metabolic syndrome and its components over time

Background: The purpose of this study was to estimate both cross-sectional sibling recurrence risk ratio (lambda(s)) and lifetime lambda(s) for the metabolic syndrome and its individual components over time among sibships in the prospectively followed-up cohorts provided by the Genetic Analysis Workshop 13. Five measures included in the operational criteria of the metabolic syndrome by the Adult Treatment Panel III were examined. A method for estimating sibling recurrence risk with correction for complete ascertainment was used to estimate the numerator, and the prevalence in the whole cohort was used as the denominator of lambda(s). Results: Considerable variability in the lambda(s) was found in terms of different time-points for the cross-sectional definition, the times of fulfilling the criterion for lifetime definition, and different components. Obesity and hyperglycemia had the highest cross-sectional lambda(s) of the five components. Both components also had the largest slopes in the linear trend of the lifetime lambda(s). However, the magnitudes of the lifetime lambda(s) were similar to that of the mean cross-sectional lambda(s), which were <2. The results of nonparametric linkage analysis showed only suggestive evidence of linkage between one marker and lifetime diagnosis of low high-density lipoprotein cholesterol and metabolic syndrome, respectively. Conclusion: The lambda(s) of the metabolic syndrome and its components varies substantially across time, and the lambda(s) of lifetime diagnosis was not necessarily larger than that of a cross-sectional diagnosis. The magnitude of lambda(s) does not predict well the maximum LOD score of linkage analysis.