Family studies

Methods

Family studies allow us to determine whether a disorder aggregates in families by examining the rate of disorder in the relatives of affected individuals (probands) and comparing this with the rate of disorder in the general population or in a control group. Alternatively we can compare the frequency of disorder in the relatives of probands with the frequency among relatives of a control group of normal individuals or those with another disorder.

There are two types of family studies. The family history method is more economical in that the psychiatric history is taken from the proband. However, given that most individuals are unlikely to know as much about family members as about themselves, this method results in an underestimate of diagnoses in relatives. A more thorough but more time-consuming approach is the family study method where all available relatives are directly interviewed.

Ascertainment

An important issue is how a family study sample is ascertained. Ideally, probands should be ascertained independently from each other. This is unlikely to pose a problem for rare disorders. However, for more common conditions where a series of cases is collected, for example, by consecutive referrals of the disorder to a particular hospital, it is possible that families included in a family study contain more than one proband. This is known as multiple incomplete ascertainment. Complete ascertainment, where all affected individuals in a given population are included is rarely possible and in most instances probands are identified after some selection process (e.g. referrals to a particular hospital). Thus, factors influencing selection, such as comorbidity and help seeking may also influence observed patterns of familial aggregation.

Age correction

For genetic studies, we are interested in the proportion of individuals who have ever had the disorder (lifetime prevalence) rather than the proportion who show the disorder at one point in time (point prevalence). However, a difficulty encountered when carrying out family studies is that the observed rates of disorder will also depend on the age of the individual, the risk period for the disorder, and whether or not the individual has lived through that risk period. Thus, some members may not yet have reached the age of risk for the disorder, some are currently unaffected but will become affected at some later point, and others may have died whilst still unaffected. The most appropriate method is to correct for age and express the rate of disorder in relatives as the morbid risk or lifetime expectancy.

There are many methods of age correction, of which Weinberg's shorter method is the most straightforward. The uncorrected frequency of affected relatives F = A/(A + U) where A = the number of affected relatives and U = the number of unaffected relatives. However, there are three types of unaffected relatives ( U): those who have yet to pass through the age of risk (u1), those within the period of risk (u2), and those who are older than the age of risk (u3). The frequency of affected relatives is then corrected by assigning weights to the three groups of affected relatives, namely 0 for u1, 0.5 for u2, and 1 for u3.

The corrected frequency of affected relatives, i.e. morbid risk, is then given as

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