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Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation.

ABSTRACT: We apply integrative approaches to expression quantitative loci (eQTLs) from 44 tissues from the Genotype-Tissue Expression project and genome-wide association study data. About 60% of known trait-associated loci are in linkage disequilibrium with a cis-eQTL, over half of which were not found in previous large-scale whole blood studies. Applying polygenic analyses to metabolic, cardiovascular, anthropometric, autoimmune, and neurodegenerative traits, we find that eQTLs are significantly enriched for trait associations in relevant pathogenic tissues and explain a substantial proportion of the heritability (40-80%). For most traits, tissue-shared eQTLs underlie a greater proportion of trait associations, although tissue-specific eQTLs have a greater contribution to some traits, such as blood pressure. By integrating information from biological pathways with eQTL target genes and applying a gene-based approach, we validate previously implicated causal genes and pathways, and propose new variant and gene associations for several complex traits, which we replicate in the UK BioBank and BioVU.

SUBMITTER: Gamazon ER

PROVIDER: S-EPMC6248311 | biostudies-literature | 2018 Jul

REPOSITORIES: biostudies-literature

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Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation.

Gamazon Eric R ER Segrè Ayellet V AV van de Bunt Martijn M Wen Xiaoquan X Xi Hualin S HS Hormozdiari Farhad F Ongen Halit H Konkashbaev Anuar A Derks Eske M EM Aguet François F Quan Jie J Nicolae Dan L DL Eskin Eleazar E Kellis Manolis M Getz Gad G McCarthy Mark I MI Dermitzakis Emmanouil T ET Cox Nancy J NJ Ardlie Kristin G KG

Nature genetics 20180628 7

We apply integrative approaches to expression quantitative loci (eQTLs) from 44 tissues from the Genotype-Tissue Expression project and genome-wide association study data. About 60% of known trait-associated loci are in linkage disequilibrium with a cis-eQTL, over half of which were not found in previous large-scale whole blood studies. Applying polygenic analyses to metabolic, cardiovascular, anthropometric, autoimmune, and neurodegenerative traits, we find that eQTLs are significantly enriched ...[more]

PMID: 29955180

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Project description:Developing population models for assessing risks to terrestrial plant species listed as threatened or endangered under the Endangered Species Act (ESA) is challenging given a paucity of data on their life histories. The purpose of this study was to develop a novel approach for identifying relatively data-rich nonlisted species that could serve as representatives for species listed under the ESA in the development of population models to inform risk assessments. We used the USDA PLANTS Database, which provides data on plants present in the US territories, to create a list of herbaceous plants. A total of 8742 species was obtained, of which 344 were listed under the ESA. Using the most up-to-date phylogeny for vascular plants in combination with a database of matrix population models for plants (COMPADRE) and cluster analyses, we investigated how listed species were distributed across the plant phylogeny, grouped listed and nonlisted species according to their life history, and identified the traits distinguishing the clusters. We performed elasticity analyses to determine the relative sensitivity of population growth rate to perturbations of species' survival, growth, and reproduction and compared these across clusters and between listed and nonlisted species. We found that listed species were distributed widely across the plant phylogeny as well as clusters, suggesting that listed species do not share a common evolution or life-history characteristics that would make them uniquely vulnerable. Lifespan and age at maturity were more important for distinguishing clusters than were reproductive traits. For clusters that were intermediate in their lifespan, listed and nonlisted species responded similarly to perturbations of their life histories. However, for clusters at either extreme of lifespan, the response to survival perturbations varied depending on conservation status. These results can be used to guide the choice of representative species for population model development in the context of ecological risk assessment. Integr Environ Assess Manag 2023;19:213-223. © 2022 The Authors. Integrated Environmental Assessment and Management published by Wiley Periodicals LLC on behalf of Society of Environmental Toxicology & Chemistry (SETAC).

Dataset Information

Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation.

Publications

Using an atlas of gene regulation across 44 human tissues to inform complex disease- and trait-associated variation.

Similar Datasets

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