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Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types.

Accepted version
Peer-reviewed

Type

Article

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Authors

Anttila, Verneri 

Abstract

We introduce an approach to identify disease-relevant tissues and cell types by analyzing gene expression data together with genome-wide association study (GWAS) summary statistics. Our approach uses stratified linkage disequilibrium (LD) score regression to test whether disease heritability is enriched in regions surrounding genes with the highest specific expression in a given tissue. We applied our approach to gene expression data from several sources together with GWAS summary statistics for 48 diseases and traits (average N = 169,331) and found significant tissue-specific enrichments (false discovery rate (FDR) < 5%) for 34 traits. In our analysis of multiple tissues, we detected a broad range of enrichments that recapitulated known biology. In our brain-specific analysis, significant enrichments included an enrichment of inhibitory over excitatory neurons for bipolar disorder, and excitatory over inhibitory neurons for schizophrenia and body mass index. Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signals.

Description

Keywords

Bipolar Disorder, Body Mass Index, Brain, Chromatin, Epigenesis, Genetic, Gene Expression, Gene Expression Profiling, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Immune System Diseases, Linkage Disequilibrium, Models, Genetic, Multifactorial Inheritance, Neurons, Schizophrenia, Tissue Distribution

Journal Title

Nat Genet

Conference Name

Journal ISSN

1061-4036
1546-1718

Volume Title

50

Publisher

Springer Science and Business Media LLC
Sponsorship
Medical Research Council (MC_UU_12015/2)