Jul 26, 2017

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

PLoS Genetics
Qiongshi LuHongyu Zhao


Continuing efforts from large international consortia have made genome-wide epigenomic and transcriptomic annotation data publicly available for a variety of cell and tissue types. However, synthesis of these datasets into effective summary metrics to characterize the functional non-coding genome remains a challenge. Here, we present GenoSkyline-Plus, an extension of our previous work through integration of an expanded set of epigenomic and transcriptomic annotations to produce high-resolution, single tissue annotations. After validating our annotations with a catalog of tissue-specific non-coding elements previously identified in the literature, we apply our method using data from 127 different cell and tissue types to present an atlas of heritability enrichment across 45 different GWAS traits. We show that broader organ system categories (e.g. immune system) increase statistical power in identifying biologically relevant tissue types for complex diseases while annotations of individual cell types (e.g. monocytes or B-cells) provide deeper insights into disease etiology. Additionally, we use our GenoSkyline-Plus annotations in an in-depth case study of late-onset Alzheimer's disease (LOAD). Our analyses suggest a strong connec...Continue Reading

Mentioned in this Paper

Establishment and Maintenance of Localization
Genome-Wide Association Study
Familial Alzheimer Disease (FAD)
Immune System
Tissue Specificity
Alzheimer's Disease
Histocompatibility Testing

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