Familial sinistrality: the utility of calculating exact genotype probabilities for individuals

Measures of familial sinistrality are frequently used in neuropsychological research. However they suffer from the problem that they are essentially a global measure of phenotypes in the family, whereas they are interpreted as an indicator of the genotype of the individual concerned. In this paper it is shown how to calculate a precise probabilistic estimate of a proband's genotype, given a particular genetic model of handedness, using all of the information available in a family tree. Example calculations are provided for a range of families with one or two sinistral relatives. Genotype probabilities are also calculated for a large population data set (the National Childhood Encephalopathy Study) and it is shown that familial sinistrality does not account for all of the variability present in the genotype probabilities, and that genotype probabilities provide an additional prediction of individual sinistrality after taking familial sinistrality into account, whereas all of the information in familial sinistrality is accounted for by the genotype probabilities. Finally it is shown how genotype probabilities can be used to assess whether there is heterozygote advantage for a characteristic, and using this method it is suggested that there is no support for heterozygotes having higher intellectual ability than homozygotes.