Next Article in Journal
Enrichment Environment Positively Influences Depression- and Anxiety-Like Behavior in Serotonin Transporter Knockout Rats through the Modulation of Neuroplasticity, Spine, and GABAergic Markers
Next Article in Special Issue
Whole Exome Sequence Analysis Provides Novel Insights into the Genetic Framework of Childhood-Onset Pulmonary Arterial Hypertension
Previous Article in Journal
Mandibulofacial Dysostosis Attributed to a Recessive Mutation of CYP26C1 in Hereford Cattle
Previous Article in Special Issue
DNA Damage and Repair in Pulmonary Arterial Hypertension
Article

Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension

1
National Heart and Lung Institute, Hammersmith Campus, Imperial College London, London SW7 2BU, UK
2
Department of Medicine, University of Cambridge, Cambridge CB2 3AX, UK
3
Pulmonary Vascular Disease Unit, Royal Papworth Hospital NHS Foundation Trust, Cambridge CB2 0AY, UK
4
NIHR BioResource-Rare Diseases, Cambridge, CB2 0QQ, UK
5
Department of Haematology, University of Cambridge, Cambridge CB2 3AX, UK
6
Sheffield Institute for Translational Neuroscience, University of Sheffield, Sheffield S10 2TN, UK
7
Sheffield Bioinformatics Core, University of Sheffield, Sheffield S10 2TN, UK
8
Department of Infection, Immunity & Cardiovascular Disease, University of Sheffield, Sheffield S10 2TN, UK
9
Department of Clinical and Experimental Medicine, University of Surrey, Guildford GU2 7XH, UK
10
Department of Metabolism, Digestion and Reproduction, Imperial College London, London SW7 2BU, UK
*
Author to whom correspondence should be addressed.
Members listed in the Supplementary Materials.
Genes 2020, 11(11), 1247; https://doi.org/10.3390/genes11111247
Received: 10 September 2020 / Revised: 14 October 2020 / Accepted: 21 October 2020 / Published: 22 October 2020
(This article belongs to the Special Issue Genetics and Genomics of Pulmonary Arterial Hypertension)
Expression quantitative trait loci (eQTL) can provide a link between disease susceptibility variants discovered by genetic association studies and biology. To date, eQTL mapping studies have been primarily conducted in healthy individuals from population-based cohorts. Genetic effects have been known to be context-specific and vary with changing environmental stimuli. We conducted a transcriptome- and genome-wide eQTL mapping study in a cohort of patients with idiopathic or heritable pulmonary arterial hypertension (PAH) using RNA sequencing (RNAseq) data from whole blood. We sought confirmation from three published population-based eQTL studies, including the GTEx Project, and followed up potentially novel eQTL not observed in the general population. In total, we identified 2314 eQTL of which 90% were cis-acting and 75% were confirmed by at least one of the published studies. While we observed a higher GWAS trait colocalization rate among confirmed eQTL, colocalisation rate of novel eQTL reported for lung-related phenotypes was twice as high as that of confirmed eQTL. Functional enrichment analysis of genes with novel eQTL in PAH highlighted immune-related processes, a suspected contributor to PAH. These potentially novel eQTL specific to or active in PAH could be useful in understanding genetic risk factors for other diseases that share common mechanisms with PAH. View Full-Text
Keywords: expression quantitative trait locus; eQTL; pulmonary arterial hypertension; blood; genetics expression quantitative trait locus; eQTL; pulmonary arterial hypertension; blood; genetics
Show Figures

Figure 1

MDPI and ACS Style

Ulrich, A.; Otero-Núñez, P.; Wharton, J.; Swietlik, E.M.; Gräf, S.; Morrell, N.W.; Wang, D.; Lawrie, A.; Wilkins, M.R.; Prokopenko, I.; Rhodes, C.J.; on behalf of The NIHR BioResource—Rare Diseases Consortium; UK PAH Cohort Study Consortium. Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension. Genes 2020, 11, 1247. https://doi.org/10.3390/genes11111247

AMA Style

Ulrich A, Otero-Núñez P, Wharton J, Swietlik EM, Gräf S, Morrell NW, Wang D, Lawrie A, Wilkins MR, Prokopenko I, Rhodes CJ, on behalf of The NIHR BioResource—Rare Diseases Consortium, UK PAH Cohort Study Consortium. Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension. Genes. 2020; 11(11):1247. https://doi.org/10.3390/genes11111247

Chicago/Turabian Style

Ulrich, Anna, Pablo Otero-Núñez, John Wharton, Emilia M. Swietlik, Stefan Gräf, Nicholas W. Morrell, Dennis Wang, Allan Lawrie, Martin R. Wilkins, Inga Prokopenko, Christopher J. Rhodes, on behalf of The NIHR BioResource—Rare Diseases Consortium, and UK PAH Cohort Study Consortium. 2020. "Expression Quantitative Trait Locus Mapping in Pulmonary Arterial Hypertension" Genes 11, no. 11: 1247. https://doi.org/10.3390/genes11111247

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop