Christopher A. Odhams
A5063982664- Systemic Lupus Erythematosus Research
- interferon and immune responses
- RNA Research and Splicing
- SARS-CoV-2 and COVID-19 Research
- RNA and protein synthesis mechanisms
- Genetics and Neurodevelopmental Disorders
- Cancer Genomics and Diagnostics
- Epigenetics and DNA Methylation
- Genetic Associations and Epidemiology
- RNA regulation and disease
- Genomics and Rare Diseases
- RNA modifications and cancer
- Atherosclerosis and Cardiovascular Diseases
- Diabetes and associated disorders
- COVID-19 Clinical Research Studies
- Genomic variations and chromosomal abnormalities
- Cytokine Signaling Pathways and Interactions
- Liver Disease Diagnosis and Treatment
- Genetic factors in colorectal cancer
- Genetic and Kidney Cyst Diseases
- Protein Tyrosine Phosphatases
- CRISPR and Genetic Engineering
- Cancer-related molecular mechanisms research
- Metabolism and Genetic Disorders
- Galectins and Cancer Biology
Maastricht University
2025
Genomics England
2019-2024
King's College London
2016-2023
Oklahoma Medical Research Foundation
2023
National Institute of Neurological Disorders and Stroke
2023
National Institutes of Health
2023
DuPont (United States)
2023
Dupont Hospital
2023
University of Toronto
2022
Queen Mary University of London
2019-2022
Abstract Critical COVID-19 is caused by immune-mediated inflammatory lung injury. Host genetic variation influences the development of illness requiring critical care 1 or hospitalization 2–4 after infection with SARS-CoV-2. The GenOMICC (Genetics Mortality in Care) study enables comparison genomes from individuals who are critically ill those population controls to find underlying disease mechanisms. Here we use whole-genome sequencing 7,491 compared 48,400 discover and replicate 23...
Extrachromosomal DNA (ecDNA) is a major contributor to treatment resistance and poor outcome for patients with cancer
Several strands of evidence question the dogma that human mitochondrial DNA (mtDNA) is inherited exclusively down maternal line, most recently in three families where several individuals harbored a 'heteroplasmic haplotype' consistent with biparental transmission. Here we report similar genetic signature 7 11,035 trios, allelic fractions 5-25%, implying inheritance mtDNA 0.06% offspring. However, analysing nuclear whole genome sequence, observe likely large rare or unique...
Systemic lupus erythematosus (SLE) is an autoimmune disease, characterised by increased expression of type I interferon (IFN)-regulated genes and a striking sex imbalance towards females. Through combined genetic, in silico, vitro, ex vivo approaches, we define CXorf21, gene hitherto unknown function, which escapes X-chromosome inactivation, as candidate underlying the Xp21.2 SLE association. We demonstrate that CXorf21 IFN-response sexual dimorphism magnified immunological challenge....
The identification of causal variants in sequencing studies remains a considerable challenge that can be partially addressed by new gene-specific knowledge. Here, we integrate measures how essential gene is to supporting life, as inferred from viability and phenotyping screens performed on knockout mice the International Mouse Phenotyping Consortium essentiality carried out human cell lines. We propose cross-species classification across Full Spectrum Intolerance Loss-of-function (FUSIL)...
Using three European and two Chinese genome-wide association studies (GWAS), we investigated the performance of genetic risk scores (GRSs) for predicting susceptibility severity systemic lupus erythematosus (SLE), using renal disease as a proxy severity. We used four GWASs to test GRS both cross validating within population between populations. The in SLE prediction was evaluated by receiver operating characteristic (ROC) curves. then analyzed polygenic nature statistically. also partitioned...
The development of computational methods to assess pathogenicity pre-messenger RNA splicing variants is critical for diagnosis human disease. We assessed the capability eight algorithms, and a consensus approach, prioritize 249 uncertain significance (VUSs) that underwent functional analyses. algorithms differentiate VUSs away from immediate splice site as being 'pathogenic' or 'benign' likely have substantial impact on diagnostic testing. show SpliceAI best single strategy in this regard,...
Studies attempting to functionally interpret complex-disease susceptibility loci by GWAS and eQTL integration have predominantly employed microarrays quantify gene-expression. RNA-Seq has the potential discover a more comprehensive set of eQTLs illuminate underlying molecular consequence. We examine functional outcome 39 variants associated with Systemic Lupus Erythematosus (SLE) through data from TwinsUK microarray cohort in lymphoblastoid cell lines. use conditional analysis Bayesian...
PurposeDetermining the role of DYNC2H1 variants in nonsyndromic inherited retinal disease (IRD).MethodsGenome and exome sequencing were performed for five unrelated cases IRD with no identified variant. In vitro assays developed to validate (fibroblast assay, induced pluripotent stem cell [iPSC] derived organoids, a dynein motility assay).ResultsFour novel (V1, g.103327020_103327021dup; V2, g.103055779A>T; V3, g.103112272C>G; V4, g.103070104A>C) one previously reported variant (V5,...
Lamins are the major component of nuclear lamina, maintaining structural integrity nucleus. Lamin A/C variants well established to cause a spectrum disorders ranging from myopathies progeria, termed laminopathies. Phenotypes resulting in LMNB1 and LMNB2 have been much less clearly defined.
Cardiomyopathy (CMP) is a heritable disorder. Over 50% of cases are gene-elusive on clinical gene panel testing. The contribution variants in non-coding DNA elements that result cryptic splicing and regulate expression has not been explored. We analyzed whole-genome sequencing (WGS) data discovery cohort 209 pediatric CMP patients 1953 independent replication genomes exomes. searched for protein-coding variants, predicted to affect the function or genes. Thirty-nine percent harbored...
The omnigenic model of complex disease stipulates that the majority heritability will be explained by effects common variation on genes in periphery core pathways. Rare variant associations, expected to explain far less heritability, may enriched and thus instrumental understanding pathogenesis their potential therapeutic targets. Here, using complementary whole-exome sequencing, high-density imputation, vitro cellular assays, we identify candidate systemic lupus erythematosus (SLE). Using...
PurposeWe aimed to define a novel autosomal recessive neurodevelopmental disorder, characterize its clinical features, and identify the underlying genetic cause for this condition.MethodsWe performed detailed characterization of 19 individuals from nine unrelated, consanguineous families with disorder. We used genome/exome sequencing approaches, linkage cosegregation analyses disease-causing variants, we three-dimensional molecular in silico analysis predict causality variants where...
Abstract Genetic variants in chromatin regulators are frequently found neurodevelopmental disorders, but their effect disease etiology is rarely determined. Here, we uncover and functionally define pathogenic the modifier EZH1 as cause of dominant recessive disorders 19 individuals. encodes one two alternative histone H3 lysine 27 methyltransferases PRC2 complex. Unlike other subunits, which involved cancers developmental syndromes, implication human development largely unknown. Using...
Abstract Background Findings from previous gastric cancer microbiome studies have been conflicting, potentially due to patient and/or tumor heterogeneity. The intratumoral and its relationship with clinicopathological variables not yet characterized in detail. We hypothesized that variation microbial abundance, alpha diversity, composition is related characteristics. Methods Metagenomic analysis of 529 GC samples was performed, including whole exome sequencing data Cancer Genome Atlas (TCGA)...
Abstract Motile and non-motile cilia are associated with mutually-exclusive genetic disorders. propel sperm or extracellular fluids, their dysfunction causes primary ciliary dyskinesia. Non-motile serve as sensory/signalling antennae on most cell types, disruption single-organ ciliopathies such retinopathies multi-system syndromes. CFAP20 is a ciliopathy candidate known to modulate motile in unicellular eukaryotes. We demonstrate that zebrafish, cfap20 required for function, C. elegans ,...
As part of the 100,000 Genomes Project, we set out to assess potential viability and clinical impact reporting genetic variants associated with drug-induced toxicity for patients cancer recruited whole-genome sequencing (WGS) as a genomic medicine service. Germline WGS from 76,805 participants was analyzed pharmacogenetic (PGx) in four genes (DPYD, NUDT15, TPMT, UGT1A1) induced by five drugs used treatment (capecitabine, fluorouracil, mercaptopurine, thioguanine, irinotecan). Linking data...
Genome sequencing was first offered clinically in the UK through 100,000 Genomes Project (100KGP). Analysis restricted to predefined gene panels associated with patient's phenotype. However, rely on clearly characterised phenotypes and risk missing diagnoses outside of panel(s) applied. We propose a complementary method rapidly identify pathogenic variants, including those missed by 100KGP methods.
Abstract Critical illness in COVID-19 is caused by inflammatory lung injury, mediated the host immune system. We and others have shown that genetic variation influences development of requiring critical care 1 or hospitalisation 2;3;4 following SARS-Co-V2 infection. The GenOMICC (Genetics Mortality Care) study recruits critically-ill cases compares their genomes with population controls order to find underlying disease mechanisms. Here, we use whole genome sequencing statistical fine mapping...
TSPEAR variants cause autosomal recessive ectodermal dysplasia (ARED) 14. The function of is unknown. clinical features, the mutation spectrum, and underlying mechanisms ARED14 are poorly understood. Combining data from new previously published individuals established that primarily characterized by dental anomalies such as conical tooth cusps hypodontia, like those seen in with WNT10A-related odontoonychodermal dysplasia. AlphaFold-predicted structure-based analysis showed most pathogenic...