Tissue-specific characterization of DNA methylation (DNAm) is needed to understand its role in gene regulation and its relevance to complex traits. We generated array-based DNAm profiles for 987 human samples from the Genotype-Tissue Expression (GTEx) project, representing 9 tissue types and 424 subjects. We characterized methylome and transcriptome correlations (eQTMs), genetic regulation in cis (mQTLs and eQTLs) across tissues, and e/mQTLs links to complex traits. With this DNAm-focused integrative analysis, we contribute to the understanding of molecular regulatory mechanisms in human tissues and their impact on complex traits.
Includes code for DNAm processing with ChAMP(v.2.8.6) and minfi(1.36.0), available at Bioconductor https://www.bioconductor.org/.
Includes code for primary QTL detection using FastQTL(v.2.184). The adaptation of FastQTL is available at https://github.com/broadinstitute/gtex-pipeline/tree/master/qtl. Scripts for conditional QTL mapping have been adapted from https://github.com/funpopgen/multiple_eqtl_mapping scripts.
Includes code for cross-tissue QTL mapping by leveraging QTL signal across tissues with mashr. mashr is available at https://github.com/stephenslab/mashr.
Includes code for QTL-annotation enrichment analysis using torus. torus is available at https://github.com/xqwen/torus.
Includes code for single-tissue and cross-tissue eQTM mapping by leveraging eQTM signal across tissues with mashr. mashr is available at https://github.com/stephenslab/mashr.
Includes code for QTL-GWAS colocalization analysis using coloc, fastenloc and hyprcoloc. fastenloc is available at https://github.com/xqwen/fastenloc. coloc is available at https://github.com/chr1swallace/coloc/. hyprcoloc is available at https://github.com/jrs95/hyprcoloc.
Includes code to generate manuscript figures. Data can be found at https://figshare.com/projects/DNA_methylation_QTL_mapping_across_diverse_human_tissues_provides_molecular_links_between_genetic_variation_and_complex_traits/149524