Knowledge of the number of causative loci is necessary to estimate the power of mapping studies of complex diseases. IN this paper we re-examine theory developed by Risch (1990a) and its implications for estimating the number L of causative loci affection a complex inherited disease. We first show that methods based on Risch's analysis can produce estimates of L that are inconsistent with the observed population prevalence of the disease. We demonstrate this point by showing that the maximum likelihood estimate for L produced by the method of Farrall and Holder (1992) for cleft lip/cleft palate data is not consistent with the prevalence and develop a maximum likelihood method for estimating L that uses the entire distribution of numbers of affected individuals in families containing an affected individual. This method avoids the potential inconsistences of the Risch method and has greater precision. We apply our method to data on cleft palate/cleft lip (CLCP) and schizophrenia.

TR Number: 
2002-21
Paul Schliekelman and Montgomery Slatkin
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