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Chunk #13 — Incorporating biological information

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Critical Issues in the Inclusion of Genetic and Epigenetic Information in Prevention and Intervention Trials.
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Great advances are occurring in evaluating functional significance of genomic regions and variants. Variations found by genome sequencing can be evaluated based on functional predictions, relevance to developmental mechanisms, frequency in population and disease databases, previous GWAS evidence, or known effect on expression. Noncoding variants can be evaluated based on epigenetic signatures derived from specific resources including ENCODE and Braincloud. Existing expression and methylation data to allow the discovery eQTLs and meQTLs at specific developmental periods in brain is available in BrainCloud (Colantuoni et al., 2011; Jaffe et al., 2014; Numata et al., 2012). Relevant functional data, frequently freely available, will allow for more prudent hypothesis testing than is currently routine and wFDR allows one to place a higher prior probability on genetic variants with prior evidence of function relevant to the trait of interest.