Effect of fragile X on physical and intellectual traits estimated by pedigree analysis

A maximum likelihood scoring technique for analysis of pedigree data, which allows for estimation of random effects (variance components) concurrently with other "fixed" effects in a quantitative trait, was applied to establish the effect of the fragile X condition in the variation of intellectual and physical traits. In 52 fragile X families, intellectual status was represented by measures of vocabulary knowledge (PPVT) and of nonverbal visuospatial skills (BDT), and physical status by a combined physical (anthropometric) score, and jaw length. The fixed effects included fragile X and sex and their interaction on the mean and covariances between relatives for the intellectual and physical scores. The random effects included environmental (common and individual) and genetic (additive and dominance) components. Different genetic models were tested by the likelihood ratio criterion, and the maximum likelihood parameters for each of the three scores were based on the most appropriate models. The effect of fragile X on the mean values was found to be significant for all the traits, and much more conspicuous in male than in female individuals, the effects in the PPVT and the anthropometric score being intercorrelated. The effect of fragile X on growth of a single physical trait relative to height was demonstrated using jaw length as an example. We have also demonstrated an effect of fragile X on genetic (additive) variance, as well as on the mean of the BDT score, and the effect of age on the nongenetic variance of PPVT, and jaw length.