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Genetic Epidemiology
Article . 2011 . Peer-reviewed
License: Wiley TDM
Data sources: Crossref
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Genetic variance components estimation for binary traits using multiple related individuals

Authors: Charalampos, Papachristou; Carole, Ober; Mark, Abney;

Genetic variance components estimation for binary traits using multiple related individuals

Abstract

Understanding and modeling genetic or nongenetic factors that influence susceptibility to complex traits has been the focus of many genetic studies. Large pedigrees with known complex structure may be advantageous in epidemiological studies since they can significantly increase the number of factors whose influence on the trait can be estimated. We propose a likelihood approach, developed in the context of generalized linear mixed models, for modeling dichotomous traits based on data from hundreds of individuals all of whom are potentially correlated through either a known pedigree or an estimated covariance matrix. Our approach is based on a hierarchical model where we first assess the probability of each individual having the trait and then formulate a likelihood assuming conditional independence of individuals. The advantage of our formulation is that it easily incorporates information from pertinent covariates as fixed effects and at the same time takes into account the correlation between individuals that share genetic background or other random effects. The high dimensionality of the integration involved in the likelihood prohibits exact computations. Instead, an automated Monte Carlo expectation maximization algorithm is employed for obtaining the maximum likelihood estimates of the model parameters. Through a simulation study we demonstrate that our method can provide reliable estimates of the model parameters when the sample size is close to 500. Implementation of our method to data from a pedigree of 491 Hutterites evaluated for Type 2 diabetes (T2D) reveal evidence of a strong genetic component to T2D risk, particularly for younger and leaner cases.

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Keywords

Adult, Male, Likelihood Functions, Molecular Epidemiology, Models, Genetic, Genetic Variation, Middle Aged, Pedigree, Young Adult, Diabetes Mellitus, Type 2, North America, Ethnicity, Linear Models, Humans, Computer Simulation, Female, Genetic Predisposition to Disease, Monte Carlo Method, Algorithms

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selected citations
These citations are derived from selected sources.
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
5
Average
Average
Average
bronze