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Bayes factors in complex genetics.

ABSTRACT: The past few years have seen tremendous progress in our understanding of the genetics underlying complex disease, with associated variants being identified in dozens of traits. Despite the fact that this growing body of empirical evidence unequivocally shows the necessity for extreme levels of significance and large samples sizes, the reasoning behind these requirements is not always appreciated. As genome-wide association studies reach the limits of their resolution in the search for rarer and weaker effects, the need for appropriate design and interpretation will become ever more important. If the genetic analysis of complex disease is to avoid accumulating false positive claims, as it has in the past, then researchers will need to allow for less tangible variables such as power and prior odds rather than relying exclusively on significance when assessing the results of these studies. In this review, the basic foundations of association testing are explained from a Bayesian perspective and the potential benefits of Bayes factors as a means of measuring the weight of evidence in support of an association are described.

SUBMITTER: Sawcer S

PROVIDER: S-EPMC2987358 | biostudies-literature | 2010 Jul

REPOSITORIES: biostudies-literature

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Bayes factors in complex genetics.

Sawcer Stephen S

European journal of human genetics : EJHG 20100224 7

The past few years have seen tremendous progress in our understanding of the genetics underlying complex disease, with associated variants being identified in dozens of traits. Despite the fact that this growing body of empirical evidence unequivocally shows the necessity for extreme levels of significance and large samples sizes, the reasoning behind these requirements is not always appreciated. As genome-wide association studies reach the limits of their resolution in the search for rarer and ...[more]

PMID: 20179745

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Project description:BackgroundThe rabbit cecum hosts and interacts with a complex microbial ecosystem that contributes to the variation of traits of economic interest. Although the influence of host genetics on microbial diversity and specific microbial taxa has been studied in several species (e.g., humans, pigs, or cattle), it has not been investigated in rabbits. Using a Bayes factor approach, the aim of this study was to dissect the effects of host genetics, litter and cage on 984 microbial traits that are representative of the rabbit microbiota.ResultsAnalysis of 16S rDNA sequences of cecal microbiota from 425 rabbits resulted in the relative abundances of 29 genera, 951 operational taxonomic units (OTU), and four microbial alpha-diversity indices. Each of these microbial traits was adjusted with mixed linear and zero-inflated Poisson (ZIP) models, which all included additive genetic, litter and cage effects, and body weight at weaning and batch as systematic factors. The marginal posterior distributions of the model parameters were estimated using MCMC Bayesian procedures. The deviance information criterion (DIC) was used for model comparison regarding the statistical distribution of the data (normal or ZIP), and the Bayes factor was computed as a measure of the strength of evidence in favor of the host genetics, litter, and cage effects on microbial traits. According to DIC, all microbial traits were better adjusted with the linear model except for the OTU present in less than 10% of the animals, and for 25 of the 43 OTU with a frequency between 10 and 25%. On a global scale, the Bayes factor revealed substantial evidence in favor of the genetic control of the number of observed OTU and Shannon indices. At the taxon-specific level, significant proportions of the OTU and relative abundances of genera were influenced by additive genetic, litter, and cage effects. Several members of the genera Bacteroides and Parabacteroides were strongly influenced by the host genetics and nursing environment, whereas the family S24-7 and the genus Ruminococcus were strongly influenced by cage effects.ConclusionsThis study demonstrates that host genetics shapes the overall rabbit cecal microbial diversity and that a significant proportion of the taxa is influenced either by host genetics or environmental factors, such as litter and/or cage.

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Bayes factors in complex genetics.

Publications

Bayes factors in complex genetics.

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