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Chunk #52 — ONLINE METHODS — Multiple-tissue validation results

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Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types.
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The top enrichment from our multi-tissue analysis of gene expression was validated at the system level for 33 out of 34 phenotypes, and at the tissue level for 13 out of 20 (Results). If we allowed an enrichment of any artery sample in GTEx to be validated by an enrichment of any artery sample in EN-TEx (instead of requiring strict matching of aorta, tibial artery, and coronary artery), the number of validations rose from 13 to 16. Of the four remaining results that were not validated, three were an enrichment in lung for an immunological disease; for all three diseases, the top enrichment in the analysis of gene expression (not restricting to tissues shared between GTEx and EN-TEx) was an immune category from the Franke lab dataset, and the top enrichment in the analysis of chromatin data was an immune category in the Roadmap dataset. We hypothesize that the lung samples analyzed in GTEx may have contained substantial amounts of blood and thus exhibited a gene expression signature reflecting immune activity; this is supported by a GO enrichment analysis of