Genetic Association Studies Using Complex Survey Data
Open AccessDuring the second phase of The National Health and Nutrition Examination Survey (NHANES) III (from October, 1991 to October, 1994), blood lymphocytes were collected from 7159 participants aged 12 years and older in anticipation of advances in genetic research. Linkage of the NHANES III phenotype data with this genetic information provides an opportunity to investigate the association of a wide variety of health factors with regard to genetic. National surveys such as NHANES III employ a complex, multistage, probability sampling design to select participants representative of the civilian, non-institutionalized US population. If observations within sampled clusters are correlated and the correlation is ignored, the standard errors can be underestimated. For each sampled individual, the inverse of the product of the selection probabilities across all of the stages of sampling is their sample weights. If these sample weights are correlated with the characteristics of research interest for the observations then an analysis that does not take this into account can be biased. Test procedures developed for simple random samples are generally unsuitable for the analysis of data from these complex sample designs. The classic question when looking into the genetic variations in a population is whether the population is in the state of Hardy-Weinberg Equilibrium (HWE). This dissertation develops procedures for testing departure from HWE using family data in a complex survey setting. Two kinds of study designs, i.e., population-based design and family-based design, have been used for genetic association study for simple random samples. This dissertation develops test procedures for association between a candidate gene and disease using population-based complex survey data with and without the use of family structure information.
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