Systematic tissue-specific functional annotation of the human genome highlights immune-related DNA elements for late-onset Alzheimer’s disease

• DOI: 10.1371/journal.pgen.1006933
• Publication Date: 2017-07-24T13:49:46Z
• Authors: Qiongshi Lu; Ryan L. Powles; Sarah Abdallah; Derek Ou; Qian Wang; Yiming Hu; Yisi Lu; Wei Liu; Boyang Li; Shubhabrata Mukhe...; Paul K. Crane; Hongyu Zhao
• Keywords: Epigenomics; 0301 basic medicine; Genome, Human; Molecular Sequence Annotation; QH426-470; Polymorphism, Single Nucleotide; 3. Good health; 03 medical and health sciences; Alzheimer Disease; Organ Specificity; Databases, Genetic; Genetics; Humans; Transcriptome; Research Article; Genome-Wide Association Study

Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell tissue types. However, synthesis these datasets into effective summary metrics to characterize the functional non-coding genome remains challenge. Here, we present GenoSkyline-Plus, an extension our previous work through integration expanded set annotations produce high-resolution, single annotations. After validating with catalog tissue-specific elements previously identified in literature, apply method using 127 different types atlas heritability enrichment across 45 GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power identifying biologically relevant complex diseases while individual monocytes or B-cells) provide deeper insights disease etiology. Additionally, use GenoSkyline-Plus in-depth case study late-onset Alzheimer's (LOAD). Our analyses suggest strong connection between LOAD genetic variants contained regions monocytes. Furthermore, shares similar localization SNPs monocyte-functional Parkinson's disease. Overall, demonstrate integrated at level valuable tool understanding etiology human diseases. are freely http://genocanyon.med.yale.edu/GenoSkyline.