Loukas Moutsianas
- Genetic Associations and Epidemiology
- Genomics and Rare Diseases
- Cancer Genomics and Diagnostics
- Genomic variations and chromosomal abnormalities
- Inflammatory Bowel Disease
- Genetic factors in colorectal cancer
- Immunodeficiency and Autoimmune Disorders
- SARS-CoV-2 and COVID-19 Research
- Genetic Neurodegenerative Diseases
- Mitochondrial Function and Pathology
- interferon and immune responses
- RNA modifications and cancer
- Genetics and Neurodevelopmental Disorders
- Liver Disease Diagnosis and Treatment
- Bioinformatics and Genomic Networks
- T-cell and B-cell Immunology
- RNA Research and Splicing
- RNA and protein synthesis mechanisms
- Epigenetics and DNA Methylation
- Chronic Lymphocytic Leukemia Research
- Diabetes and associated disorders
- RNA regulation and disease
- Helicobacter pylori-related gastroenterology studies
- Genetic and Kidney Cyst Diseases
- Pancreatic function and diabetes
William Harvey Research Institute
2020-2025
Queen Mary University of London
2020-2025
Genomics England
2020-2025
University of Leeds
2025
Wellcome Sanger Institute
2016-2024
Broad Institute
2024
Boston Children's Hospital
2024
Stanford University
2023
University College London
2022-2023
Hospital for Sick Children
2022-2023
Host-mediated lung inflammation is present1, and drives mortality2, in the critical illness caused by coronavirus disease 2019 (COVID-19). Host genetic variants associated with may identify mechanistic targets for therapeutic development3. Here we report results of GenOMICC (Genetics Of Mortality In Critical Care) genome-wide association study 2,244 critically ill patients COVID-19 from 208 UK intensive care units. We have identified replicated following new significant associations: on...
Background & AimsAnti–tumor necrosis factor (anti-TNF) therapies are the most widely used biologic drugs for treating immune-mediated diseases, but repeated administration can induce formation of anti-drug antibodies. The ability to identify patients at increased risk development antibodies would facilitate selection therapy and use preventative strategies.MethodsWe performed a genome-wide association study variants associated with time in discovery cohort 1240 biologic-naïve Crohn's disease...
The U.K. 100,000 Genomes Project is in the process of investigating role genome sequencing patients with undiagnosed rare diseases after usual care and alignment this research health implementation National Health Service. Other parts project focus on cancer infection.
Whole-genome sequencing (WGS) permits comprehensive cancer genome analyses, revealing mutational signatures, imprints of DNA damage and repair processes that have arisen in each patient's cancer. We performed signature analyses on 12,222 WGS tumor-normal matched pairs, from patients recruited via the UK National Health Service. contrasted our results to two independent datasets, International Cancer Genome Consortium (ICGC) Hartwig Foundation, involving 18,640 cancers total. Our add 40...
Abstract Irritable bowel syndrome (IBS) results from disordered brain–gut interactions. Identifying susceptibility genes could highlight the underlying pathophysiological mechanisms. We designed a digestive health questionnaire for UK Biobank and combined identified cases with IBS independent cohorts. conducted genome-wide association study 53,400 433,201 controls replicated significant associations in 23andMe panel (205,252 1,384,055 controls). Our confirmed six genetic loci IBS. Implicated...
Abstract Mutations in the germline generates all evolutionary genetic variation and is a cause of disease. Parental age primary determinant number new mutations an individual’s genome 1,2 . Here we analysed genome-wide sequences 21,879 families with rare diseases identified 12 individuals hypermutated between two seven times more de novo single-nucleotide variants than expected. In most (9 out 12), excess came from father. Two had drivers hypermutation, fathers carrying damaging DNA-repair...
Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is an autosomal recessive neurodegenerative disease, usually caused by biallelic AAGGG repeat expansions in RFC1. In this study, we leveraged whole genome sequencing data from nearly 10 000 individuals recruited within the Genomics England project to investigate normal pathogenic variation of RFC1 repeat. We identified three novel motifs, AGGGC (n = 6 five families), AAGGC 2 one family) AGAGG 1), associated with CANVAS...
Statistical imputation of classical HLA alleles in case-control studies has become established as a valuable tool for identifying and fine-mapping signals disease association the MHC. Imputation into diverse populations has, however, remained challenging, mainly because additional haplotypic heterogeneity introduced by combining reference panels different sources. We present an type model, HLA*IMP:02, designed to operate on multi-population panel. HLA*IMP:02 is based graphical representation...
Abstract Motivation: Genetic variation at classical HLA alleles influences many phenotypes, including susceptibility to autoimmune disease, resistance pathogens and the risk of adverse drug reactions. However, typing methods are often prohibitively expensive for large-scale studies. We previously described a method imputing from linked SNP genotype data. Here, we present modification original algorithm implemented in freely available software suite that combines local data preparation QC...
Peroxisome proliferator-activated receptor gamma (PPARG) is a master transcriptional regulator of adipocyte differentiation and canonical target antidiabetic thiazolidinedione medications. In rare families, loss-of-function (LOF) mutations in PPARG are known to cosegregate with lipodystrophy insulin resistance; the general population, common P12A variant associated decreased risk type 2 diabetes (T2D). Whether how variants defects influence T2D population remains undetermined. By sequencing...
Genome and exome sequencing in large cohorts enables characterization of the role rare variation complex diseases. Success this endeavor, however, requires investigators to test a diverse array genetic hypotheses which differ number, frequency effect sizes underlying causal variants. In study, we evaluated power gene-based association methods interrogate such hypotheses, examined implications for study design. We developed flexible simulation approach, using 1000 Genomes data, (a) generate...
Abstract The subset of patients who develop critical illness in Covid-19 have extensive inflammation affecting the lungs 1 and are strikingly different from other patients: immunosuppressive therapy benefits critically-ill patients, but may harm some non-critical cases. 2 Since susceptibility to life-threatening infections immune-mediated diseases both strongly heritable traits, we reasoned that host genetic variation identify mechanistic targets for therapeutic development Covid-19. 3...
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...