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Disease risk estimation by combining case-control data with aggregated information on the population at risk.

ABSTRACT: We propose a novel statistical framework by supplementing case-control data with summary statistics on the population at risk for a subset of risk factors. Our approach is to first form two unbiased estimating equations, one based on the case-control data and the other on both the case data and the summary statistics, and then optimally combine them to derive another estimating equation to be used for the estimation. The proposed method is computationally simple and more efficient than standard approaches based on case-control data alone. We also establish asymptotic properties of the resulting estimator, and investigate its finite-sample performance through simulation. As a substantive application, we apply the proposed method to investigate risk factors for endometrial cancer, by using data from a recently completed population-based case-control study and summary statistics from the Behavioral Risk Factor Surveillance System, the Population Estimates Program of the US Census Bureau, and the Connecticut Department of Transportation.

SUBMITTER: Chang X

PROVIDER: S-EPMC4782587 | biostudies-literature | 2015 Mar

REPOSITORIES: biostudies-literature

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Disease risk estimation by combining case-control data with aggregated information on the population at risk.

Chang Xiaohui X Waagepetersen Rasmus R Yu Herbert H Ma Xiaomei X Holford Theodore R TR Wang Rong R Guan Yongtao Y

Biometrics 20141028 1

We propose a novel statistical framework by supplementing case-control data with summary statistics on the population at risk for a subset of risk factors. Our approach is to first form two unbiased estimating equations, one based on the case-control data and the other on both the case data and the summary statistics, and then optimally combine them to derive another estimating equation to be used for the estimation. The proposed method is computationally simple and more efficient than standard ...[more]

PMID: 25351292

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Project description:BACKGROUND:In genetic studies of rare complex diseases it is common to ascertain familial data from population based registries through all incident cases diagnosed during a pre-defined enrollment period. Such an ascertainment procedure is typically taken into account in the statistical analysis of the familial data by constructing either a retrospective or prospective likelihood expression, which conditions on the ascertainment event. Both of these approaches lead to a substantial loss of valuable data. METHODOLOGY AND FINDINGS:Here we consider instead the possibilities provided by a Bayesian approach to risk analysis, which also incorporates the ascertainment procedure and reference information concerning the genetic composition of the target population to the considered statistical model. Furthermore, the proposed Bayesian hierarchical survival model does not require the considered genotype or haplotype effects be expressed as functions of corresponding allelic effects. Our modeling strategy is illustrated by a risk analysis of type 1 diabetes mellitus (T1D) in the Finnish population-based on the HLA-A, HLA-B and DRB1 human leucocyte antigen (HLA) information available for both ascertained sibships and a large number of unrelated individuals from the Finnish bone marrow donor registry. The heterozygous genotype DR3/DR4 at the DRB1 locus was associated with the lowest predictive probability of T1D free survival to the age of 15, the estimate being 0.936 (0.926; 0.945 95% credible interval) compared to the average population T1D free survival probability of 0.995. SIGNIFICANCE:The proposed statistical method can be modified to other population-based family data ascertained from a disease registry provided that the ascertainment process is well documented, and that external information concerning the sizes of birth cohorts and a suitable reference sample are available. We confirm the earlier findings from the same data concerning the HLA-DR3/4 related risks for T1D, and also provide here estimated predictive probabilities of disease free survival as a function of age.

Dataset Information

Disease risk estimation by combining case-control data with aggregated information on the population at risk.

Publications

Disease risk estimation by combining case-control data with aggregated information on the population at risk.

Similar Datasets

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