using functional annotation for the empirical determination of bayes factors for genome-wide association study analysis使用功能注释的全基因组关联研究的经验贝叶斯的确定因素分析.pdfVIP

Using Functional Annotation for the Empirical Determination of Bayes Factors for Genome-Wide Association Study Analysis 1,2 3,4 4 1 Jo Knight *, Michael R. Barnes , Gerome Breen , Michael E. Weale 1 Department of Medical and Molecular Genetics, King’s College London School of Medicine, London, United Kingdom, 2 National Institute for Health Research (NIHR), Biomedical Research Centre Guy’s and St. Thomas’ NHS Foundation Trust and King’s College London, London, United Kingdom, 3 Computational Biology, GlaxoSmithKline, Stevenage, United Kingdom, 4 Social, Genetic and Developmental Psychiatry Centre, Institute of Psychiatry, King’s College London School of Medicine, London, United Kingdom Abstract A genome wide association study (GWAS) typically results in a few highly significant ‘hits’ and a much larger set of suggestive signals (‘near-hits’). The latter group are expected to be a mixture of true and false associations. One promising strategy to help separate these is to use functional annotations for prioritisation of variants for follow-up. A key task is to determine which annotations might prove most valuable. We address this question by examining the functional annotations of previously published GWAS hits. We explore three annotation categories: non-synonymous SNPs (nsSNPs), promoter SNPs and cis expression quantitative trait loci (eQTLs) in open chromatin regions. We demonstrate that GWAS hit SNPs are enriched for these three functional categories, and that it would be appropriate to provide a higher weighting for such SNPs when performing Bayesian association analyses. For GWAS studies, our analyses suggest the use of a Bayes Factor of about 4 for cis eQTL SNPs within reg