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Cross-tissue eQTL enrichment of associations in schizophrenia
- Source :
- PLoS ONE, Vol 13, Iss 9, p e0202812 (2018), PloS one, vol 13, iss 9, Bettella, F; Brown, AA; Smeland, OB; Wang, Y; Witoelar, A; Demur, AAB; et al.(2018). Cross-tissue eQTL enrichment of associations in schizophrenia. PLOS ONE, 13(9). doi: 10.1371/journal.pone.0202812. UC San Diego: Retrieved from: http://www.escholarship.org/uc/item/8f46r54n, PLoS ONE
- Publication Year :
- 2018
- Publisher :
- Public Library of Science (PLoS), 2018.
-
Abstract
- The genome-wide association study of the Psychiatric Genomics Consortium identified over one hundred schizophrenia susceptibility loci. The number of non-coding variants discovered suggests that gene regulation could mediate the effect of these variants on disease. Expression quantitative trait loci (eQTLs) contribute to variation in levels of mRNA. Given the co-occurrence of schizophrenia and several traits not involving the central nervous system (CNS), we investigated the enrichment of schizophrenia associations among eQTLs for four non-CNS tissues: adipose tissue, epidermal tissue, lymphoblastoid cells and blood. Significant enrichment was seen in eQTLs of all tissues: adipose (β = 0.18, p = 8.8 × 10-06), epidermal (β = 0.12, p = 3.1 × 10-04), lymphoblastoid (β = 0.19, p = 6.2 × 10-08) and blood (β = 0.19, p = 6.4 × 10-06). For comparison, we looked for enrichment of association with traits of known relevance to one or more of these tissues (body mass index, height, rheumatoid arthritis, systolic blood pressure and type-II diabetes) and found that schizophrenia enrichment was of similar scale to that observed when studying diseases in the context of a more likely causal tissue. To further investigate tissue specificity, we looked for differential enrichment of eQTLs with relevant Roadmap affiliation (enhancers and promoters) and varying distance from the transcription start site. Neither factor significantly contributed to the enrichment, suggesting that this is equally distributed in tissue-specific and cross-tissue regulatory elements. Our analyses suggest that functional correlates of schizophrenia risk are prevalent in non-CNS tissues. This could be because of pleiotropy or the effectiveness of variants affecting expression in different contexts. This suggests the utility of large, single-tissue eQTL experiments to increase eQTL discovery power in the study of schizophrenia, in addition to smaller, multiple-tissue approaches. Our results conform to the notion that schizophrenia is a systemic disorder involving many tissues.
- Subjects :
- 0301 basic medicine
Physiology
Test Statistics
Gene Expression
Adipose tissue
lcsh:Medicine
Genome-wide association study
Mathematical and Statistical Techniques
0302 clinical medicine
Risk Factors
Pleiotropy
Medicine and Health Sciences
2.1 Biological and endogenous factors
Aetiology
lcsh:Science
2. Zero hunger
Genetics
Regulation of gene expression
Multidisciplinary
Chromosome Mapping
Genomics
Serious Mental Illness
Body Fluids
Blood
Phenotype
Mental Health
Adipose Tissue
Organ Specificity
Schizophrenia
Physical Sciences
Anatomy
Statistics (Mathematics)
Research Article
General Science & Technology
Immunology
Quantitative Trait Loci
Rheumatoid Arthritis
Context (language use)
Biology
Research and Analysis Methods
Autoimmune Diseases
03 medical and health sciences
Rheumatology
Mental Health and Psychiatry
Genome-Wide Association Studies
medicine
Humans
Genetic Predisposition to Disease
Statistical Methods
Arthritis
Human Genome
lcsh:R
Biology and Life Sciences
Computational Biology
Genetic Variation
Human Genetics
Promoter
Genome Analysis
medicine.disease
Brain Disorders
Biological Tissue
030104 developmental biology
Gene Expression Regulation
Genetic Loci
Expression quantitative trait loci
Clinical Immunology
lcsh:Q
Clinical Medicine
Epidermis
Mathematics
Blood Chemical Analysis
030217 neurology & neurosurgery
Genome-Wide Association Study
Subjects
Details
- Language :
- English
- ISSN :
- 19326203
- Volume :
- 13
- Issue :
- 9
- Database :
- OpenAIRE
- Journal :
- PLoS ONE
- Accession number :
- edsair.doi.dedup.....d1e6f30dc4b2dedad187f78f5d474b6c