STATISTICAL METHODS FOR GENETIC CASE CONTROL STUDIES
Project Number1R01GM055326-01A1
Contact PI/Project LeaderSCHOENFELD, DAVID ALAN
Awardee OrganizationMASSACHUSETTS GENERAL HOSPITAL
Description
Abstract Text
DESCRIPTION: Many genetic studies are based on analyzing multiple DNA
regions of cases and controls. Usually each is tested separately for
association with disease. However some diseases may require interacting
polymorphisms at several regions. Methods will be developed for determining
combinations of polymorphisms that increase the risk of disease when DNA
from cases and controls have been analyzed for polymorphisms at multiple
regions. These methods will be used to determine combinations of
polymorphisms of genetic fragments in the coding regions of linked HLA genes
that increase the risk of Insulin Dependent Diabetes Mellitus (IDDM) Methods
will also be developed for designing such studies and choosing sample sizes.
Suppose that the DNA of cases and controls can be classified in terms of
polymorphisms at multiple DNA regions. The problem is to find a smaller
number of regions and corresponding polymorphisms so that the risk of
disease is high when an individual has this combination of polymorphisms.
This problem has three facets. 1. Finding a small number of DNA regions
and polymorphisms that optimally predict disease status. 2. Expressing the
uncertainty of this determination. 3. Incorporating samples where not
every region is analyzed. A modern, computer intensive, statistical
technique, the Data Augmentation Algorithm will be used to incorporate data
from individuals who have not had every region analyzed and to
simultaneously quantify our uncertainty about the true probability of each
combination of polymorphisms among normal and diseased individuals in the
population that we sampled. The algorithm produces multiple samples of the
probabilities that a diseased and a no-diseased individual have each
possible combination of polymorphisms. Each is a sample from the posterior
distribution, i.e., each sample is an equally likely value of the set of
population probabilities. The variation from sample to sample expresses the
uncertainty due to the sample size and the fact that some data was missing.
For each sample we select all the combinations of two or three polymorphisms
that are good at predicting disease. The frequency with which a combination
is selected estimates the posterior probability that the combination is a
good predictor.
Public Health Relevance Statement
Data not available.
NIH Spending Category
No NIH Spending Category available.
Project Terms
DNAcomputer data analysisdata managementdisease /disorder proneness /riskgenetic polymorphismhistocompatibility antigenshuman population geneticsinsulin dependent diabetes mellitusmathematical modelmodel design /developmentnucleic acid sequencestatistics /biometry
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