Familial aggregation is generally the first source of evidence that genetic factors may play a role in a disorder. The patterns of genetic factors underlying a disorder can be inferred from the extent to which patterns of familial resemblance adhere to the expectations of Mendelian laws of inheritance. Familial patterns may also be used to estimate the heritability of a trait or disorder, defined as the extent to which variation in a phenotype is attributable to genetic factors (see Box 1). Family studies can also be used to examine the extent to which familial/genetic factors may underlie sex differences in transmission or manifestation of a particular disorder. 67 In the case of a female‐preponderant disorder, relatives of affected males would be expected to show higher rates of the disorder than do relatives of affected females. If the rates do not differ between the relatives of males and females with the disorder, then we can conclude that the sex difference in a particular condition cannot be attributed to familial or genetic factors.
