Hierarchical Modeling of the Relation Between Sequence Variants and a Quantitative Trait: Addressing Multiple Comparison and Population Stratification Issues
Autor: | Lee-Lian Kim, John S. Witte, Bonnie A. Fijal |
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Rok vydání: | 2001 |
Předmět: |
0301 basic medicine
Candidate gene Epidemiology Population Computational biology 030105 genetics & heredity Quantitative trait locus Biology Population stratification Hierarchical database model 03 medical and health sciences Quantitative Trait Heritable Linear regression Humans Genetic Predisposition to Disease education Genetics (clinical) education.field_of_study Models Genetic Chromosome Mapping Genetic Variation Contrast (statistics) Genetics Population 030104 developmental biology Multiple comparisons problem Regression Analysis |
Zdroj: | Genetic Epidemiology. 21:S668-S673 |
ISSN: | 0741-0395 |
DOI: | 10.1002/gepi.2001.21.s1.s668 |
Popis: | When analyzing the relation between genetic sequence information and disease traits, false-positive associations can arise due to multiple comparisons and population stratification. In an attempt to address these issues, we incorporate into a conventional analytic model higher-level--or "prior"--models that use additional information to improve estimates while allowing for differing population structures. We apply this hierarchical model to simulated data from the Genetic Analysis Workshop 12. We focus on the effects of common candidate gene sequence variants on quantitative risk factor 5 (Q5) levels. In particular, we compare the regression coefficients (and 95% confidence intervals) obtained from conventional (one-stage) analyses versus the corresponding results from the hierarchical analyses. When examining either the marry-ins or all subjects in the general and isolate populations, the conventional model detected numerous sites in candidate genes 1-5 and 7 that had statistically significant regression coefficients (alpha level = 0.05). In contrast, our hierarchical model primarily only detected associations for variants in candidate gene 2, which is the casual gene for Q5. |
Databáze: | OpenAIRE |
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