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Testing Concordance of Clinical Characteristics in Familial Studies with Application to Inflammatory Bowel Diseases

The etiology of chronic Inflammatory Bowel Diseases (IBD) remains unknown, with both genetic and environmental risk factors having been implicated. A recent collaborative study of IBD provides clinical data from families with three or more affected first‐degree relatives. The scientific question is whether specific clinical characteristics aggregate among affected individuals within families. Gastroenterological researchers have examined the number of concordant familial pairs in familial aggregation studies, but methods and results have been discrepant. This article investigates concepts of concordance and gives a comprehensive statistical treatment for testing concordance of various clinical traits in familial studies. For dichotomous traits, the distribution of this statistic under the null hypothesis of no familial aggregation is obtained by three methods: asymptotic, probability generating function, and permutation. The permutation method is extended to analyze aggregation for non‐dichotomous traits and co‐aggregations between two traits. We apply the permutation method to analyze the aforementioned multiply‐affected IBD family data. Evidence is found for familial clustering of various traits, some of which are not revealed in existing studies. Such analyses provide a basis for investigating the dependence of trait aggregation upon genetic or environmental risk factors. (© 2007 WILEY‐VCH Verlag GmbH & Co. KGaA, Weinheim)