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  • Title: Estimating morbidity risks in relatives: the effect of reduced fertility.
    Author: Risch N.
    Journal: Behav Genet; 1983 Sep; 13(5):441-51. PubMed ID: 6667223.
    Abstract:
    Various methods have been given for calculating morbidity risks in relatives. When estimating morbidity risks for parents, an additional complication needs to considered, i.e., that the disease may affect fertility thereby biasing the parent sample (usually in favor of those who are unaffected). The effect of reduced fertility was first noted in 1955 in schizophrenics by Essen-Moller. A simple method for adjusting the observed morbid risk to parents, whicch requires fewer assumptions than Essen-Moller's method, is presented. A method is outlined for determining the potential effect of reduced fertility on the estimation of morbid risk for other types of relatives -- siblings, grandchildren, and nieces and nephews. The morbid risk to parents of probands is a reflection of the following parameters: A, prevalence of the disorder in the population; mo, mean number of children produced by an unaffected individual; ml, mean number of children produced by an affected individual; to, probability that the child of an unaffected individual is affected; and tl, probability that the child of an affected individual is affected. It is assumed that ml includes both the effect of nonmarriage and the effect of reduced fertility within marriage. The tl parameter is to be estimated from the observed risk to parents. The accuracy of tl depends only on the precision of knowledge of ml/mo, the ratio of mean number of children produced by affected individuals vso normals. The Essen-Moller method requires knowing the relative fertility for affected individuals both before and after disease onset, as well as the ages at onset with respect to the birth of the proband for affected parents of probands. To consider morbid risk to parents by sex, it is necessary to define sex specific parameters. That the observed risk to siblings may also be diminished due to reduced fertility of affecteds may be seen as follows. Suppose the risk to a sib when 1 of the proband's parents is also affected is greater than when both parents are unaffected. An affected parent produces fewer children overall than when both parents are normal. Thus, a proband with an affected parent has fewer sibs than one without an affected parent. To determine the effect of reduced fertility on the risk to the grandchildren of an affected individual, the 2 cases where the intervening parent is affected or normal must be considered. The risk to nieces and nephews of a proband may depend on whether the parent of the niece/nephew (i.e., proband's sibling) is affected or not. The only risk estimate that is free of fertility effects is the risk to children. As shown here, risks to other relatives can be substantially influenced, depending on the particular relationship involved. One should be cautious about combining risks to all 1st-degree relatives as well as concerned with the age adjustment method used in calculating morbid risks.
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