Two-Stage Bayesian Approach for GWAS With Known Genealogy

ABSTRACT

Genome-wide association studies (GWAS) aim to assess relationships between single nucleotide polymorphisms (SNPs) and diseases. They are one of the most popular problems in genetics, and have some peculiarities given the large number of SNPs compared to the number of subjects in the study. Individuals might not be independent, especially in animal breeding studies or genetic diseases in isolated populations with highly inbred individuals. We propose a family-based GWAS model in a two-stage approach comprising a dimension reduction and a subsequent model selection. The first stage, in which the genetic relatedness between the subjects is taken into account, selects the promising SNPs. The second stage uses Bayes factors for comparison among all candidate models and a random search strategy for exploring the space of all the regression models in a fully Bayesian approach. A simulation study shows that our approach is superior to Bayesian lasso for model selection in this setting. We also illustrate its performance in a study on Beta-thalassemia disorder in an isolated population from Sardinia. Supplementary Material describing the implementation of the method proposed in this article is available online.

KEYWORDS:

• Bayes factor
• Beta-thalassemia disorder
• Gaussian Markov random field
• Kinship coefficient
• Model selection
• Robust prior distribution

Supplementary Material

Appendix: Details on the implementation to enable readers to apply the article’s proposed method to their own data. (supplem.pdf)

Acknowledgments

The authors thank the editor, associate editor, and referees for their useful comments that improved very much the original version of the article, and also Mario Pirastu and Maria Pina Concas for providing the data.

Additional information

Funding

This article was partially funded by MTM2016-77501-P research grant and ECO2012-38442, RYC-2012-11455 projects from the Spanish Ministry of Economy and Competitiveness, and CRP-59903 from Regione Autonoma della Sardegna (Italy).