@article {Boix2021-br,
	title = {Regulatory genomic circuitry of human disease loci by integrative epigenomics},
	journal = {Nature},
	volume = {590},
	number = {7845},
	year = {2021},
	pages = {300{\textendash}307},
	abstract = {Annotating the molecular basis of human disease remains an unsolved challenge, as 93\% of disease loci are non-coding and gene-regulatory annotations are highly incomplete1-3. Here we present EpiMap, a compendium comprising 10,000 epigenomic maps across 800 samples, which we used to define chromatin states, high-resolution enhancers, enhancer modules, upstream regulators and downstream target genes. We used this resource to annotate 30,000 genetic loci that were associated with 540 traits4, predicting trait-relevant tissues, putative causal nucleotide variants in enriched tissue enhancers and candidate tissue-specific target genes for each. We partitioned multifactorial traits into tissue-specific contributing factors with distinct functional enrichments and disease comorbidity patterns, and revealed both single-factor monotropic and multifactor pleiotropic loci. Top-scoring loci frequently had multiple predicted driver variants, converging through multiple enhancers with a common target gene, multiple genes in common tissues, or multiple genes and multiple tissues, indicating extensive pleiotropy. Our results demonstrate the importance of dense, rich, high-resolution epigenomic annotations for the investigation of complex traits.},
	keywords = {My Papers},
	author = {Boix, Carles A and James, Benjamin T and Park, Yongjin P and Meuleman, Wouter and Kellis, Manolis}
}
