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Nat Genet DOI:10.1038/s41588-018-0081-4

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

Publication TypeJournal Article
Year of Publication2018
AuthorsFinucane, HK, Reshef, YA, Anttila, V, Slowikowski, K, Gusev, A, Byrnes, A, Gazal, S, Loh, P-R, Lareau, C, Shoresh, N, Genovese, G, Saunders, A, Macosko, E, Pollack, S, Perry, JRB, Buenrostro, JD, Bernstein, BE, Raychaudhuri, S, McCarroll, S, Neale, BM, Price, AL
Corporate AuthorsBrainstorm Consortium
JournalNat Genet
Volume50
Issue4
Pages621-629
Date Published2018 04
ISSN1546-1718
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.

DOI10.1038/s41588-018-0081-4
Pubmed

http://www.ncbi.nlm.nih.gov/pubmed/29632380?dopt=Abstract

Alternate JournalNat. Genet.
PubMed ID29632380
PubMed Central IDPMC5896795
Grant ListR01 MH094714 / MH / NIMH NIH HHS / United States
R21 MH103877 / MH / NIMH NIH HHS / United States
U01 CA194393 / CA / NCI NIH HHS / United States
U01 MH103365 / MH / NIMH NIH HHS / United States
U01 MH103392 / MH / NIMH NIH HHS / United States
U01 MH103346 / MH / NIMH NIH HHS / United States
MC_UU_12015/2 / / Medical Research Council / United Kingdom
R01 MH105472 / MH / NIMH NIH HHS / United States
U01 MH103340 / MH / NIMH NIH HHS / United States
U01 MH103339 / MH / NIMH NIH HHS / United States
R01 AR063759 / AR / NIAMS NIH HHS / United States
U01 HG009379 / HG / NHGRI NIH HHS / United States
UH2 AR067677 / AR / NIAMS NIH HHS / United States
R21 MH102791 / MH / NIMH NIH HHS / United States
R01 MH107649 / MH / NIMH NIH HHS / United States
R01 MH105898 / MH / NIMH NIH HHS / United States
R21 MH105881 / MH / NIMH NIH HHS / United States
R01 MH109978 / MH / NIMH NIH HHS / United States
P50 MH106934 / MH / NIMH NIH HHS / United States