Abstract
Most genetic epidemiological study designs fall into one of two categories: family based and population-based (case–control). However, recent advances in statistical genetics call for study designs that combine these two approaches. We describe the household contact study design as we have applied it in our several years of study of the epidemiology of tuberculosis. Though we highlight its applicability for genetic epidemiological studies of infectious diseases, there are many facets of this design that are appealing for modern genetic studies, including the simultaneous enrollment of related and unrelated individuals, closely and distantly related individuals, collection of extensive epidemiologic and phenotypic data, and evaluation of effects of shared environment and gene by environment interaction. These study design characteristics are particularly appealing for current sequencing studies.
Highlights
The advantages of family studies for genetic epidemiology have long been established (Stein and Elston, 2009)
We describe the household contact study design as we have applied it in our several years of study of the epidemiology of tuberculosis
We provide an overview of our household contact (HHC) study of TB and its advantages for genetic epidemiological studies, in light of study designs best suited to identify rare genetic variants
Summary
The advantages of family studies for genetic epidemiology have long been established (Stein and Elston, 2009). Household contact studies for genetics identification of individuals with different phenotypes or stages of TB infection in a household including: (1) exposed and uninfected, (2) exposed and infected without disease, (3) recent infection, and (4) active TB. These different household phenotypes or categories can provide the basis to compare genetic factors associated with TB infection and disease. As all of these stages of infection and disease are diagnosed, both the index case and his/her contacts receive appropriate clinical care and treatment, which is an immediate benefit to all study participants. There is flexibility for collection of biological samples and a longitudinal component to observe changes in phenotypes and biomarkers
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