| Title: | Leveraging molecular quantitative trait loci to understand the genetic architecture of diseases and complex traits |
| Journal: | Nature Genetics |
| Published: | 25 Jun 2018 |
| Pubmed: | https://pubmed.ncbi.nlm.nih.gov/29942083/ |
| DOI: | https://doi.org/10.1038/s41588-018-0148-2 |
| URL: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6030458 |
| Citations: | 167 (38 in last 2 years) as of 8 Aug 2024 |
Publication 5319
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Abstract
There is increasing evidence that many risk loci found using genome-wide association studies are molecular quantitative trait loci (QTLs). Here we introduce a new set of functional annotations based on causal posterior probabilities of fine-mapped molecular cis-QTLs, using data from the Genotype-Tissue Expression (GTEx) and BLUEPRINT consortia. We show that these annotations are more strongly enriched for heritability (5.84× for eQTLs; P = 1.19 × 10−31) across 41 diseases and complex traits than annotations containing all significant molecular QTLs (1.80× for expression (e)QTLs). eQTL annotations obtained by meta-analyzing all GTEx tissues generally performed best, whereas tissue-specific eQTL annotations produced stronger enrichments for blood- and brain-related diseases and traits. eQTL annotations restricted to loss-of-function intolerant genes were even more enriched for heritability (17.06×; P = 1.20 × 10−35). All molecular QTLs except splicing QTLs remained significantly enriched in joint analysis, indicating that each of these annotations is uniquely informative for disease and complex trait architectures.</p>
8 Keywords
- Disease
- Genome-Wide Association Study
- Humans
- Multifactorial Inheritance
- Phenotype
- Polymorphism, Single Nucleotide
- Quantitative Trait Loci
- Quantitative Trait, Heritable
13 Authors
- Farhad Hormozdiari
- Steven Gazal
- Bryce van de Geijn
- Hilary K. Finucane
- Chelsea J.-T. Ju
- Po-Ru Loh
- Armin Schoech
- Yakir Reshef
- Xuanyao Liu
- Luke O'Connor
- Alexander Gusev
- Eleazar Eskin
- Alkes L. Price
Enabling scientific discoveries that improve human health