A compendium of uniformly processed human gene expression and splicing quantitative trait loci

Kerimov, Nurlan; Hayhurst, James; Peikova, Kateryna; Manning, Jonathan; Walter, Peter; Kolberg, Liis; Samoviča, Marija; Sakthivel, Manoj Pandian; Kuzmin, Ivan; Trevanion, Stephen J.; Burdett, Tony; Jupp, Simon; Parkinson, Helen; Papatheodorou, Irene; Yates, Andrew D; Zerbino, Daniel R.; Alasoo, Kaur

doi:10.1038/s41588-021-00924-w

Cited by 245 publications

(260 citation statements)

References 113 publications

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“…Colocalizations with a posterior probability >0.8 were considered successful colocalizations. eQTL data from all tissues except microglia were obtained from the eQTL catalog [41]. The microglia data were obtained from Young et al [42].…”

Section: Methodsmentioning

confidence: 99%

Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers

Jansen

Lee

Gomez‐Fonseca

et al. 2022

Preprint

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Amyloid-beta 42 (Aβ42) and phosphorylated tau (pTau) levels in cerebrospinal fluid (CSF) reflect core features of the pathogenesis of Alzheimer’s disease (AD) more directly than clinical diagnosis. Initiated by the European Alzheimer & Dementia Biobank (EADB), the largest collaborative effort on genetics underlying CSF biomarkers was established, including 31 cohorts with a total of 13,116 individuals (discovery n = 8,074; replication n = 5,042 individuals). Besides the APOE locus, novel associations with two other well-established AD risk loci were observed; CR1 was shown a locus for amyloid beta 42 (Aβ42) and BIN1 for phosphorylated Tau (pTau). GMNC and C16orf95 were further identified as loci for pTau, of which the latter is novel. Clustering methods exploring the influence of all known AD risk loci on the CSF protein levels, revealed 4 biological categories (amyloid, astrocyte, processing & migration, and migration & motility) suggesting multiple Aβ42 and pTau related biological pathways involved in the etiology of AD. In functional follow-up analyses, GMNC and C16orf95 both associated with lateral ventricular volume, implying an overlap in genetic etiology for tau levels and brain ventricular volume.

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Section: Methodsmentioning

confidence: 99%

Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers

Jansen

Lee

Gomez‐Fonseca

et al. 2022

Preprint

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“…We now source eQTL data from the eQTL Catalogue ( 25 ), which uniformly processes data from a wide range of studies. These are displayed using a Manhattan track in the Regulation section of the Gene view, and the 'Genes and Regulation' section of the Variant view.…”

Section: Comprehensive Genome Annotation For Reference Vertebrate Speciesmentioning

confidence: 99%

Ensembl 2022

Cunningham

Allen

et al. 2021

Nucleic Acids Research

Self Cite

1,418

938

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Ensembl (https://www.ensembl.org) is unique in its flexible infrastructure for access to genomic data and annotation. It has been designed to efficiently deliver annotation at scale for all eukaryotic life, and it also provides deep comprehensive annotation for key species. Genomes representing a greater diversity of species are increasingly being sequenced. In response, we have focussed our recent efforts on expediting the annotation of new assemblies. Here, we report the release of the greatest annual number of newly annotated genomes in the history of Ensembl via our dedicated Ensembl Rapid Release platform (http://rapid.ensembl.org). We have also developed a new method to generate comparative analyses at scale for these assemblies and, for the first time, we have annotated non-vertebrate eukaryotes. Meanwhile, we continually improve, extend and update the annotation for our high-value reference vertebrate genomes and report the details here. We have a range of specific software tools for specific tasks, such as the Ensembl Variant Effect Predictor (VEP) and the newly developed interface for the Variant Recoder. All Ensembl data, software and tools are freely available for download and are accessible programmatically.

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“…This region loops to the promoter of the short isoform of ZMIZ1 in EBV EBNA2+ Ramos cells. rs1250567 is a strong eQTL for ZMIZ1 in both EBV-immortalized lymphoblast cell lines (P-value: 1.76 × 10 −4 ) and whole blood (P-value: 2.21 × 10 −4 ; eQTL catalog) (Kerimov et al 2021; Supplemental Table S15). ZMIZ1 expression levels are threefold lower in EBV EBNA2+ Ramos cells compared to uninfected Ramos cells, consistent with a previous report by Fewings et al (2017) describing decreased ZMIZ1 protein expression in MS patient blood samples.…”

Section: Allele-dependent Ebna2 Mechanisms At Autoimmune-associated Risk Locimentioning

confidence: 99%

Epstein–Barr virus nuclear antigen 2 extensively rewires the human chromatin landscape at autoimmune risk loci

et al. 2021

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The interplay between environmental and genetic factors plays a key role in the development of many autoimmune diseases. In particular, the Epstein–Barr virus (EBV) is an established contributor to multiple sclerosis, lupus, and other disorders. Previously, we showed that the EBV nuclear antigen 2 (EBNA2) transactivating protein occupies up to half of the risk loci for a set of seven autoimmune disorders. To further examine the mechanistic roles played by EBNA2 at these loci on a genome-wide scale, we globally examined gene expression, chromatin accessibility, chromatin looping, and EBNA2 binding in a B cell line that was (1) uninfected, (2) infected with a strain of EBV lacking EBNA2, or (3) infected with a strain that expresses EBNA2. We identified more than 400 EBNA2-dependent differentially expressed human genes and more than 5000 EBNA2 binding events in the human genome. ATAC-seq analysis revealed more than 2000 regions in the human genome with EBNA2-dependent chromatin accessibility, and HiChIP data revealed more than 1700 regions where EBNA2 altered chromatin looping interactions. Autoimmune genetic risk loci were highly enriched at the sites of these EBNA2-dependent chromatin-altering events. We present examples of autoimmune risk genotype–dependent EBNA2 events, nominating genetic risk mechanisms for autoimmune risk loci such as ZMIZ1. Taken together, our results reveal important interactions between host genetic variation and EBNA2-driven disease mechanisms. Further, our study highlights a critical role for EBNA2 in rewiring human gene regulatory programs through rearrangement of the chromatin landscape and nominates these interactions as components of genetic mechanisms that influence the risk of multiple autoimmune diseases.

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A compendium of uniformly processed human gene expression and splicing quantitative trait loci

Cited by 245 publications

References 113 publications

Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers

Genome-wide meta-analysis for Alzheimer’s disease cerebrospinal fluid biomarkers

Ensembl 2022

Epstein–Barr virus nuclear antigen 2 extensively rewires the human chromatin landscape at autoimmune risk loci

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