Examining the Relative Influence of Familial, Genetic, and Environmental Covariate Information in Flexible Risk Models
Description
We present a novel method for examining the relative influence of familial, genetic and environmental covariate information in flexible nonparametric risk models. Our goal is investigating the relative importance of these three sources of information as they are associated with a particular outcome. To that end, we developed a method for incorporating arbitrary pedigree information in a smoothing spline ANOVA (SS-ANOVA) model. By expressing pedigree data as a positive semidefinite kernel matrix, the SS-ANOVA model is able to estimate a log-odds ratio as a multicomponent function of several variables: one or more functional components representing information from environmental covariates and/or genetic marker data and another representing pedigree relationships. We report a case study on models for retinal pigmentary abnormalities in the Beaver Dam Eye Study (BDES). Our model verifies known facts about the epidemiology of this eye lesion - found in eyes with early age-related macular degeneration (AMD) - and shows significantly increased predictive ability in models that include all three of the genetic, environmental and familial data sources. The case study also shows that models that contain only two of these data sources, that is, pedigree-environmental covariates or pedigree-genetic markers, or environmental covariates-genetic markers, have comparable predictive ability, while less than the model with all three. This result is consistent with the notions that genetic marker data encodes - at least partly - pedigree data, and that familial correlations encode shared environment data as well.
| Slides | |
| 0:00 | Examining the Relative Influence of Familial, Genetic and Covariate Information In Flexible Risk Models |
| 8:30 | Abstract |
| 12:00 | Outline |
| 14:15 | The Log Likelihood for Bernoulli responses |
| 15:55 | Penalized Log Likelihood Estimate |
| 17:19 | Reproducing Kernel Hilbert Spaces (RKHS) |
| 20:14 | ANOVA Decomposition of Functions of Several Variables |
| 21:17 | ANOVA Decomposition of Functions of Several Variables (continued) (1) |
| 22:04 | ANOVA Decomposition of Functions of Several Variables (continued) (2) |
| 23:47 | ANOVA Decomposition of Functions of Several Variables (continued) (3) |
| 25:03 | ANOVA Decomposition of Functions of Several Variables (continued) (4) |
| 26:21 | SS-ANOVA Model in the Beaver Dam Eye Study (1) |
| 27:19 | SS-ANOVA Model in the Beaver Dam Eye Study (2) |
| 28:48 | SS-ANOVA Model in the Beaver Dam Eye Study (3) |
| 31:42 | SS-ANOVA Model in the Beaver Dam Eye Study (4) |
| 33:54 | Modeling E/C, genetic and pedigree data in an extended SS-ANOVA model |
| 36:33 | A Pedigree from BDES |
| 37:35 | A Relationship (Sub)Graph From the Pedigree |
| 38:45 | Relationship Data Encoded with RKE |
| 40:34 | Relationship Data Encoded With RKE (continued) |
| 43:41 | Embedding of Pedigree by RKE |
| 44:32 | Relationship Data Encoded With RKE (continued) |
| 46:38 | Qualitative Results |
| 47:20 | Comparing Models by Their Area Under the (ROC) Curve (AUC) |
| 47:54 | Results |
| 48:28 | Summary and Conclusions |
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