Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types
Hilary K. Finucane, Yakir Reshef, Verneri Anttila, Kamil Slowikowski, Alexander Gusev, Andrea Byrnes, Steven Gazal, Po‐Ru Loh et al.. Nature Genetics, 2018-04-01
Topic: Genetics and APOE
Genetics can provide a systematic approach to discovering the tissues and cell types relevant for a complex disease or trait. Identifying these tissues and cell types is critical for following up on non-coding allelic function, developing ex-vivo models, and identifying therapeutic targets. Here, we analyze gene expression data from several sources, including the GTEx and PsychENCODE consortia, together with genome-wide association study (GWAS) summary statistics for 48 diseases and traits with an average sample size of 169,331, to identify disease-relevant tissues and cell types. We develop and apply an approach that uses stratified LD score regression to test whether disease heritability is enriched in regions surrounding genes with the highest specific expression in a given tissue. We detect tissue-specific enrichments at FDR < 5% for 34 diseases and traits across a broad range of tissues that recapitulate known biology. In our analysis of traits with observed central nervous system enrichment, we detect an enrichment of neurons over other brain cell types for several brain-related traits, enrichment of inhibitory over excitatory neurons for bipolar disorder but excitatory over inhibitory neurons for schizophrenia and body mass index, and enrichments in the cortex for schizophrenia and in the striatum for migraine. In our analysis of traits with observed immunological enrichment, we identify enrichments of T cells for asthma and eczema, B cells for primary biliary cirrhosis, and myeloid cells for Alzheimer's disease, which we validated with independent chromatin data. Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signal.
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APA 7th
Finucane, H. K., Reshef, Y., Anttila, V., Slowikowski, K., Gusev, A., Byrnes, A., et al. (2018). Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nature Genetics. https://doi.org/10.1038/s41588-018-0081-4
Vancouver
Finucane HK, Reshef Y, Anttila V, Slowikowski K, Gusev A, Byrnes A, et al. Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types. Nature Genetics. 2018. doi:10.1038/s41588-018-0081-4. PMID: 29632380.
BibTeX
@article{finucane2018-29632380,
author = {Finucane, Hilary K. and Reshef, Yakir and Anttila, Verneri and Slowikowski, Kamil and Gusev, Alexander and Byrnes, Andrea and Gazal, Steven and Loh, Po‐Ru and others},
title = {{Heritability enrichment of specifically expressed genes identifies disease-relevant tissues and cell types}},
journal = {Nature Genetics},
year = {2018},
doi = {10.1038/s41588-018-0081-4},
pmid = {29632380},
url = {https://doi.org/10.1038/s41588-018-0081-4}
}
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Key findings
- Our results demonstrate that our polygenic approach is a powerful way to leverage gene expression data for interpreting GWAS signal.
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Study details
- Evidence strengthLow
How this study scored 45/100
Published in a leading specialty journal. Scored zero for study design, sample size, effect reported, studied in people and randomised / blinded because the record does not state it. We have no data on journal's citation record, times cited, citations per year, impact for its field and year, cited by studies here, still being cited, senior author's track record, institution's track record and multi-centre collaboration, so those were left out: it earned 26 of the 58 points we could judge it on, which is 45 out of 100.
| Component | Points | Why |
|---|---|---|
| Journal tier | 9 / 10 | Tier 2 — leading specialty journal (Nature Genetics) |
| Journal's citation record | — / 4 | No journal record from OpenAlex — left out of this score |
| Study design | 0 / 12 | No study design recorded — scores zero, not guessed (not stated in the record — scored 0) |
| Strength of evidence | 1 / 5 | Rated “low” in our summary |
| Peer-review validation | 10 / 10 | Peer-reviewed. Published as an article in a named peer-reviewed journal. |
| How recent | 2 / 5 | 2018 — within 10 year(s) of the newest study here |
| Sample size | 0 / 4 | Participant count not stated — scores zero (not stated in the record — scored 0) |
| Effect reported | 0 / 3 | No effect size reported — scores zero (not stated in the record — scored 0) |
| Studied in people | 0 / 3 | Not stated whether this was studied in people — scores zero (not stated in the record — scored 0) |
| Randomised / blinded | 0 / 2 | No randomisation or blinding stated — scores zero (not stated in the record — scored 0) |
| Times cited | — / 7 | No citation count (not found in OpenAlex) — left out of this score |
| Citations per year | — / 5 | No citation count or no year — left out of this score |
| Impact for its field and year | — / 6 | No field-weighted citation impact (OpenAlex has none yet) — left out of this score |
| Cited by studies here | — / 6 | Not yet checked against this library's citation graph — left out of this score |
| Still being cited | — / 4 | No yearly citation counts — left out of this score |
| Senior author's track record | — / 4 | Senior author's record not available — left out of this score |
| Institution's track record | — / 3 | No institution listed in OpenAlex — left out of this score |
| Multi-centre collaboration | — / 3 | Institutions not listed — left out of this score |
| Indexed in PubMed | 2 / 2 | Indexed in PubMed (PMID 29632380) |
| Free to read | 2 / 2 | Free to read |
| Points | 26 / 58 | Scored on 11 of 20 parts. We have no data for the rest, so they are left out: 26 of the 58 points we could judge it on is 45 out of 100. |
| Total | 45 / 100 | — |
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