All Outputs (27)

Patient and Public Involvement and Engagement for PhD Students (2023)
Working Paper
Gladman, J. R. F., Stocks, J., Phillips, B., Horobin, A., Wragg, A., Mundey, M., …Humes, D. (2022). Patient and Public Involvement and Engagement for PhD Students

This paper aims to provide useful advice regarding the development of skills for patient and public involvement and engagement (PPIE) in research. The authors of this paper comprise experienced PhD supervisors and trainers, researchers leading PPIE a... Read More about Patient and Public Involvement and Engagement for PhD Students.

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease (2022)
Journal Article
Holstege, H., Hulsman, M., Charbonnier, C., Grenier-Boley, B., Quenez, O., Grozeva, D., …Lambert, J. (in press). Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease. Nature Genetics, https://doi.org/10.1038/s41588-022-01208-7

Alzheimer’s disease (AD), the leading cause of dementia, has an estimated heritability of approximately 70%1. The genetic component of AD has been mainly assessed using genome-wide association studies, which do not capture the risk contributed by rar... Read More about Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as risk factors for Alzheimer’s disease.

DNA methylation signatures of Alzheimer’s disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types (2022)
Journal Article
Shireby, G., Dempster, E. L., Policicchio, S., Smith, R. G., Pishva, E., Chioza, B., …Mill, J. (2022). DNA methylation signatures of Alzheimer’s disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types. Nature Communications, 13, Article 5620. https://doi.org/10.1038/s41467-022-33394-7

Alzheimer’s disease (AD) is a chronic neurodegenerative disease characterized by the progressive accumulation of amyloid-beta and neurofibrillary tangles of tau in the neocortex. We profiled DNA methylation in two regions of the cortex from 631 donor... Read More about DNA methylation signatures of Alzheimer’s disease neuropathology in the cortex are primarily driven by variation in non-neuronal cell-types.

Upregulated expression of FFAR2 and SOC3 genes is associated with gout (2022)
Journal Article
Orji, O. C., López-Domínguez, M. B., Sandoval-Plata, G., Guetta-Baranes, T., Valdes, A. M., Doherty, M., …Abhishek, A. (2023). Upregulated expression of FFAR2 and SOC3 genes is associated with gout. Rheumatology, 62(2), 977-983. https://doi.org/10.1093/rheumatology/keac360

Objective To examine the expression of Free fatty acid receptor 2 (FFAR2) and Suppressor of cytokine signalling 3 (SOCS3) genes in asymptomatic hyperuricaemia (AH), AH with MSU crystal deposition, inter-critical gout and gout flare. Methods Study... Read More about Upregulated expression of FFAR2 and SOC3 genes is associated with gout.

Are polymorphisms affecting serum urate, renal urate handling and alcohol intake associated with co-morbidities in gout cases? A case–control study using data from the UK Biobank (2022)
Journal Article
Sandoval-Plata, G., Morgan, K., & Abhishek, A. (2022). Are polymorphisms affecting serum urate, renal urate handling and alcohol intake associated with co-morbidities in gout cases? A case–control study using data from the UK Biobank. Rheumatology International, 42, 1617-1622. https://doi.org/10.1007/s00296-022-05148-7

Objective: To examine the association between common comorbidities, eGFR and loci involved in the hyperuricaemia-gout transition. Methods: This study was conducted in people with gout from the UK Biobank. Logistic regression was used to examine th... Read More about Are polymorphisms affecting serum urate, renal urate handling and alcohol intake associated with co-morbidities in gout cases? A case–control study using data from the UK Biobank.

Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as novel risk factors for Alzheimers Disease (2022)
Working Paper
Holstege, H., Hulsman, M., Charbonnier, C., Grenier-Boley, B., Quenez, O., Grozeva, D., …Lambert, J. Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as novel risk factors for Alzheimers Disease

The genetic component of Alzheimer’s disease (AD) has been mainly assessed using Genome Wide Association Studies (GWAS), which do not capture the risk contributed by rare variants. Here, we compared the gene-based burden of rare damaging variants in... Read More about Exome sequencing identifies rare damaging variants in ATP8B4 and ABCA1 as novel risk factors for Alzheimers Disease.

Meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex (2021)
Journal Article
Shireby, G., Smith, R. G., Pishva, E., Smith, A. R., Roubroeks, J. A. Y., Hannon, E., …Lunnon, K. (2021). Meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex. Nature Communications, 12, Article 3517. https://doi.org/10.1038/s41467-021-23243-4

Epigenome-wide association studies of Alzheimer’s disease have highlighted neuropathology-associated DNA methylation differences, although existing studies have been limited in sample size and utilized different brain regions. Here, we combine data f... Read More about Meta-analysis of epigenome-wide association studies in Alzheimer's disease highlights novel differentially methylated loci across cortex.

Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores (2021)
Journal Article
de Rojas, I., Moreno-Grau, S., Tesi, N., Grenier-Boley, B., Andrade, V., Jansen, I. E., …PGC-ALZ consortia. (2021). Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores. Nature Communications, 12(1), Article 3417. https://doi.org/10.1038/s41467-021-22491-8

Genetic discoveries of Alzheimer’s disease are the drivers of our understanding, and together with polygenetic risk stratification can contribute towards planning of feasible and efficient preventive and curative clinical trials. We first perform a l... Read More about Common variants in Alzheimer’s disease and risk stratification by polygenic risk scores.

Variants in urate transporters, ADH1B, GCKR and MEPE genes associate with transition from asymptomatic hyperuricaemia to gout: Results of the first gout versus asymptomatic hyperuricaemia GWAS in Caucasians using data from the UK Biobank (2021)
Journal Article
Sandoval-Plata, G., Morgan, K., & Abhishek, A. (2021). Variants in urate transporters, ADH1B, GCKR and MEPE genes associate with transition from asymptomatic hyperuricaemia to gout: Results of the first gout versus asymptomatic hyperuricaemia GWAS in Caucasians using data from the UK Biobank. Annals of the Rheumatic Diseases, 80(9), 1220-1226. https://doi.org/10.1136/annrheumdis-2020-219796

Objectives: To perform a genome-wide association study (GWAS) of gout cases vs. asymptomatic hyperuricaemia (AH) controls, and gout cases vs. normouricaemia controls, and to generate a polygenic risk score (PRS) to determine gout-case vs. AH-control... Read More about Variants in urate transporters, ADH1B, GCKR and MEPE genes associate with transition from asymptomatic hyperuricaemia to gout: Results of the first gout versus asymptomatic hyperuricaemia GWAS in Caucasians using data from the UK Biobank.

Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture (2021)
Journal Article
Shakkottai, V. G., Goldstein, D. S., Gan-Or, Z., Flanagan, M. E., Sidransky, E., The American Genome Center, …Morgan, K. (2021). Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture. Nature Genetics, 53, 294-303. https://doi.org/10.1038/s41588-021-00785-3

The genetic basis of Lewy body dementia (LBD) is not well understood. Here, we performed whole-genome sequencing in large cohorts of LBD cases and neurologically healthy controls to study the genetic architecture of this understudied form of deme... Read More about Genome sequencing analysis identifies new loci associated with Lewy body dementia and provides insights into its genetic architecture.

Association between serum urate, gout and comorbidities: a case–control study using data from the UK Biobank (2020)
Journal Article
Sandoval-Plata, G., Nakafero, G., Chakravorty, M., Morgan, K., & Abhishek, A. (2021). Association between serum urate, gout and comorbidities: a case–control study using data from the UK Biobank. Rheumatology, 60(7), 3243-3251. https://doi.org/10.1093/rheumatology/keaa773

Objectives To examine the association between comorbidities and serum urate (SU), gout and comorbidities, and to determine whether the association between gout and comorbidities is independent of SU. Methods We performed a case-control study using UK... Read More about Association between serum urate, gout and comorbidities: a case–control study using data from the UK Biobank.

Genetic variants in glutamate-, A??, and tau-related pathways determine polygenic risk for Alzheimer's disease (2020)
Journal Article
Lawingco, T., Chaudhury, S., Brookes, K. J., Guetta-Baranes, T., Guerreiro, R., Bras, J., …Morgan, K. (2021). Genetic variants in glutamate-, Aβ−, and tau-related pathways determine polygenic risk for Alzheimer's disease. Neurobiology of Aging, 101, 299.e13-299.e21. https://doi.org/10.1016/j.neurobiolaging.2020.11.009

© 2020 Elsevier Inc. Synapse loss is an early event in late-onset Alzheimer's disease (LOAD). In this study, we have assessed the capacity of a polygenic risk score (PRS) restricted to synapse-encoding loci to predict LOAD. We used summary statistics... Read More about Genetic variants in glutamate-, A??, and tau-related pathways determine polygenic risk for Alzheimer's disease.

The Epistasis Project: a multi-cohort study of the effects of BDNF, DBH and SORT1 epistasis on Alzheimer's disease risk (2019)
Journal Article
Belbin, O., Morgan, K., Medway, C., Warden, D., Cortina-Borja, M., van Duijn, C. M., …Lehmann, D. J. (2019). The Epistasis Project: a multi-cohort study of the effects of BDNF, DBH and SORT1 epistasis on Alzheimer's disease risk. Journal of Alzheimer's Disease, 68(4), 1535-1547. https://doi.org/10.3233/JAD-181116

Pre-synaptic secretion of brain-derived neurotrophic factor (BDNF) from noradrenergic neurons may protect the Alzheimer’s disease (AD) brain from amyloid pathology. While the BDNF polymorphism (rs6265) is associated with faster cognitive decline and... Read More about The Epistasis Project: a multi-cohort study of the effects of BDNF, DBH and SORT1 epistasis on Alzheimer's disease risk.

Genetic variability in response to amyloid beta deposition influences Alzheimer’s disease risk (2019)
Journal Article
Salih, D. A., Bayram, S., Guelfi, S., Reynolds, R. H., Shoai, M., Ryten, M., …Hardy, J. (2019). Genetic variability in response to amyloid beta deposition influences Alzheimer’s disease risk. Brain Communications, 1(1), Article fcz022. https://doi.org/10.1093/braincomms/fcz022

Genome-wide association studies of late-onset Alzheimer’s disease risk have previously identified genes primarily expressed in microglia that form a transcriptional network. Using transgenic mouse models of amyloid deposition, we previously showed th... Read More about Genetic variability in response to amyloid beta deposition influences Alzheimer’s disease risk.

Observations of extensive gene expression differences in the cerebellum and potential relevance to Alzheimer’s disease (2018)
Journal Article
Chappell, S., Patel, T., Guetta-Baranes, T., Sang, F., Francis, P. T., Morgan, K., & Brookes, K. J. (2018). Observations of extensive gene expression differences in the cerebellum and potential relevance to Alzheimer’s disease. BMC Research Notes, 11(1), https://doi.org/10.1186/s13104-018-3732-8

Objectives In order to determine how gene expression is altered in disease it is of fundamental importance that the global distribution of gene expression levels across the disease-free brain are understood and how differences between tissue types... Read More about Observations of extensive gene expression differences in the cerebellum and potential relevance to Alzheimer’s disease.

Gene-Based Analysis in HRC Imputed Genome Wide Association Data Identifies Three Novel Genes For Alzheimer’s Disease (2018)
Working Paper
Baker, E., Sims, R., Leonenko, G., Frizzati, A., Harwood, J., Grozeva, D., …EADI Consortium. Gene-Based Analysis in HRC Imputed Genome Wide Association Data Identifies Three Novel Genes For Alzheimer’s Disease

A novel POLARIS gene-based analysis approach was employed to compute gene-based polygenic risk score (PRS) for all individuals in the latest HRC imputed GERAD (N cases=3332 and N controls=9,832) data using the International Genomics of Alzheimer's Pr... Read More about Gene-Based Analysis in HRC Imputed Genome Wide Association Data Identifies Three Novel Genes For Alzheimer’s Disease.

A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease (2018)
Journal Article
Hartl, D., May, P., Gu, W., Mayhaus, M., Pichler, S., Spaniol, C., …Riemenschneider, M. (2020). A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease. Molecular Psychiatry, 25, 629–639. https://doi.org/10.1038/s41380-018-0091-8

Common variants of about 20 genes contributing to AD risk have so far been identified through genome-wide association studies (GWAS). However, there is still a large proportion of heritability that might be explained by rare but functionally importan... Read More about A rare loss-of-function variant of ADAM17 is associated with late-onset familial Alzheimer disease.

Analysis of shared heritability in common disorders of the brain (2018)
Journal Article
Anttila, V., Bulik-Sullivan, B., Finucane, H. K., Walters, R. K., Bras, J., Duncan, L., …Neale, B. M. (2018). Analysis of shared heritability in common disorders of the brain. Science, 360(6395), Article eaap8757. https://doi.org/10.1126/science.aap8757

Disorders of the brain can exhibit considerable epidemiological comorbidity and often share symptoms, provoking debate about their etiologic overlap. We quantified the genetic sharing of 25 brain disorders from genome-wide association studies of 265,... Read More about Analysis of shared heritability in common disorders of the brain.

Genotyping of the Alzheimer’s disease Genome-Wide Association Study index single nucleotide polymorphisms in the Brains for Dementia research cohort (2018)
Journal Article
Brookes, K. J., McConnell, G., Williams, K., Chaudhury, S. R., Madhan, G., Patel, T., …Morgan, K. (2018). Genotyping of the Alzheimer’s disease Genome-Wide Association Study index single nucleotide polymorphisms in the Brains for Dementia research cohort. Journal of Alzheimer's Disease, 64(2), https://doi.org/10.3233/JAD-180191

The Brains for Dementia Research project is a recently established cohort which aims to provide brain tissue for research purposes from neuropathologically defined samples. Here we present the findings from our analysis on the 19 established GWAS in... Read More about Genotyping of the Alzheimer’s disease Genome-Wide Association Study index single nucleotide polymorphisms in the Brains for Dementia research cohort.

Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease (2018)
Journal Article
Kucukkilic, E., Brookes, K., Barber, I., Guetta-Baranes, T., Morgan, K., & Hollox, E. (in press). Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease. Human Genetics, https://doi.org/10.1007/s00439-018-1883-2

Single nucleotide variants (SNVs) within and surrounding the complement receptor 1 (CR1) gene show some of the strongest genome-wide association signals with late-onset Alzheimer’s disease. Some studies have suggested that this association signal is... Read More about Complement receptor 1 gene (CR1) intragenic duplication and risk of Alzheimer’s disease.