An integrative genomics approach for non-invasive diagnostic biomarkers discovery in IgA nephropathy

Lead Research Organisation: Imperial College London
Department Name: School of Public Health

Abstract

IgAN is the commonest form of glomerulonephritis worldwide. Currently the diagnosis can only be made by kidney biopsy, and a single biopsy provides limited information about the future risk of kidney failure. In addition, since this disease can run in families, there is a need for a test to predict whether relatives of patients might develop the disease. We aim to use genetic analysis, together with clinical measurements and disease markers, such as deglycosylated IgA to develop a way of predicting which patients are at risk of progression and which relatives are at risk of developing the disease.

Technical Summary

A) Family-based and population-based linkage analysis
B) Identification of quantitative trait loci (QTL) responsible for deglycosylated IgA1 serum levels;
C) Stratification using susceptibility genetic variants (HLA haplotypes, structural variants across the CFH-CFHR);
D) Resequencing through NGS of a selected subsample of informative families
E) Variants Validation
F) Identification of biomarkers for IgAN and Bayesian Model

Planned Impact

IgA nephropathy is the most common form of primary glomerulonephritis, leading to end-stage renal disease in up to 40% of patients, who thus require dialysis or kidney transplant within 20 years of renal biopsy-proven diagnosis. This is a significant economic burden on patients and healthcare system in the UK. This translational medicine project will better elucidate the pathogenesis of the disease and also ultimately provide a refined non-invasive tool useful for screening at-risk relatives and for stratification of IgA nephropathy patients in order to achieve their personalized treatment.

Publications

10 25 50
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Cox SN (2017) Multiple rare genetic variants co-segregating with familial IgA nephropathy all act within a single immune-related network. in Journal of internal medicine

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Dotz V (2021) O- and N-Glycosylation of Serum Immunoglobulin A is Associated with IgA Nephropathy and Glomerular Function. in Journal of the American Society of Nephrology : JASN

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Falchi M (2014) Low copy number of the salivary amylase gene predisposes to obesity. in Nature genetics

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Lomax-Browne HJ (2017) IgA1 Glycosylation Is Heritable in Healthy Twins. in Journal of the American Society of Nephrology : JASN

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Medjeral-Thomas N (2019) Glomerular Complement Factor H-Related Protein 5 (FHR5) Is Highly Prevalent in C3 Glomerulopathy and Associated With Renal Impairment in Kidney International Reports

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Medjeral-Thomas NR (2018) Progressive IgA Nephropathy Is Associated With Low Circulating Mannan-Binding Lectin-Associated Serine Protease-3 (MASP-3) and Increased Glomerular Factor H-Related Protein-5 (FHR5) Deposition. in Kidney international reports

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Medjeral-Thomas NR (2017) Circulating complement factor H-related proteins 1 and 5 correlate with disease activity in IgA nephropathy. in Kidney international

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Sallustio F (2015) Genome-wide scan identifies a copy number variable region at 3p21.1 that influences the TLR9 expression levels in IgA nephropathy patients. in European journal of human genetics : EJHG

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Visconti A (2017) PopPAnTe: population and pedigree association testing for quantitative data. in BMC genomics

 
Title Copy Number Variation Assay 
Description Assay used to determine the copy number of two genes CFHR1 and CFHR3 in samples. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact This assay has enabled us to determine copy numbers for 2 genes CFHR1 and CFHR3 - deletions of which are associated with protection against IgA Nephropathy. Further more accurate analyses can be carried out on the data by splitting the samples into groups based on copy number number of these genes. Our data from this assay has been included in a revised manuscript that we have submitted to Kidney International (Medjeral-Thomas et al, 2017). 
URL https://www.thermofisher.com/uk/en/home/life-science/pcr/real-time-pcr/real-time-pcr-assays/cnv-anal...
 
Title ELISA 
Description Assay to measure biological parameters in the samples collected from the patients in our study 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact We are able to measure biological parameters including antibody levels, levels of immune system proteins and glycosylation of IgA by using the ELISAs we have set up. These assays will allow us to gain extensive phenotypic information about our samples, which we can link to genetic information. 
 
Title IgA Glycomics 
Description We are collaborating with the Leiden University Medical Center and have validated high throughput glycosylation analysis of IgA variability in IgAN cases and in family-based controls. We have combined a case control study for IgAN - aimed to the identification of glycans involved in the disease and in the disease progression - and carried out a heritability study in the general population using MZ and DZ twins to understand how much of the IgA glycome is under genetic control. IgA glycomics data have been characterised in an additional sample of 2500 twins, for which multiple -omics data (including transcriptomics, epigenomics, IgG glycomics and whole serum, whole genome sequencing, gut metagenomics, metabolomics) are available. This study, which is possibly the largest glycomics experiment on IgA to date, will identify genes, pathways and environmental factors associated with IgA glycans. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact Glycomics method for the IgA molecules have been improved and tested on IgAN case control study. Glycans involved with IgAN risk and progression have been identified. Once the multi-omics analyses of the large 2500 twins sample will be completed we will get a better picture of how the IgA glycans assortment relates with the host genome and the gut microbiome composition, which are the processes involved and their metabolomics signatures. Apart from clarifying the role of IgA in IgAN development these studies will provide novel insight into the biology of IgA. 
 
Title SNP Genotyping 
Description SNP Genotyping assays were used to analyse the samples collected for this study, for the genoytpe of a SNP associated with risk of IgA nephropathy. 
Type Of Material Technology assay or reagent 
Provided To Others? No  
Impact This assay has enabled us to determine the allelic frequency of a disease associated SNP in our sample cohort. Further more accurate analyses can be carried out on the data by splitting the samples into genotypic groups. Our data from this assay has been included in a revised manuscript tat we have submitted to Kidney International (Medjeral-Thomas et al, 2017). 
URL http://www.thermofisher.com/uk/en/home/life-science/pcr/real-time-pcr/real-time-pcr-assays/snp-genot...
 
Title Causes and Predictors of Outcome in IgA Nephropathy - Database 
Description This database has been created to store experimentally generated data and clinical data about patients recruited on to our study. 
Type Of Material Database/Collection of data 
Provided To Others? No  
Impact This database ensures secure and logical storage of the data generated from our study. It will enable easy and efficient analysis of the data that is generated. 
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Aintree University Hospital NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Brighton and Sussex University Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Colchester Hospital University NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Guy's and St Thomas' NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Hull and East Yorkshire Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Lancashire Teaching Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Leeds Teaching Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Manchester University NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Mid Essex Hospital Services NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Newcastle upon Tyne Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Academic/University 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation North Bristol NHS Trust
Country United Kingdom 
Sector Academic/University 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation North Cumbria University Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Royal Cornwall Hospitals NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation Royal Devon and Exeter NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation South Tees Hospitals NHS Foundation Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description Causes and Predictors of Outcome in IgA Nephropathy 
Organisation University Hospitals of North Midlands NHS Trust
Country United Kingdom 
Sector Public 
PI Contribution Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. Working with the UKCRN, our research team was responsible for setting up the study, applying successfully for ethical approval and administration of adding additional sites to the study and arranging patient recruitment and sample transfer at these sites.
Collaborator Contribution working with the UKCRN, our partners have each facilitated the administration of the study at their sites and recruited patients with IgA Nephropathy onto the study, following informed consent.
Impact Part of our project involved the recruitment of patients with IgA Nephropathy onto a study, so we could collect samples from patients who had been informed of the study and given informed consent. In order for us to recruit our target of 300 patients, we added sites to our study in collaborations. From these collaborations we have recruited in total 334 patients with IgA Nephropathy onto our study. This is a massive achievement and excellent outcome for our research project.
Start Year 2014
 
Description European IgAN Consortium 
Organisation European IgA Nephropathy (IgAN) Consortium
Country Italy 
Sector Charity/Non Profit 
PI Contribution We have been collaborating with the European IgAN Consortium for the Whole Exome Sequencing analysis of extended families segregating IgAN. Rare variants have been identified, the manuscript is under review
Collaborator Contribution The European IgAN Consortium has identified a number of extended families segregating igAN and lab work has been carried out for the identification and validation of rare variants involved in the disease.
Impact paper PMID 25293716 manuscript under revision: "Rare Genetic Variants Implicated in Innate and Adaptive Immunity Co-Segregate with Familial IgA Nephropathy"
Start Year 2014
 
Description Glycomics Analysis of IgAN Patients and Healthy Twins 
Organisation Leiden University Medical Center
Country Netherlands 
Sector Academic/University 
PI Contribution We have contributed serum samples from patients with IgA Nephropathy and serum samples from healthy twins for glycomic analysis.
Collaborator Contribution Our partners are performing glycomic analysis on the samples we have contributed.
Impact This collaboration is on-going and the data has not been analysed yet. Our aim is to analyse then disseminate the data through publications, whilst correlating the data with patient outcome and genetics.
Start Year 2015
 
Description Peking University 
Organisation Peking University First Hospital
Country China 
Sector Hospitals 
PI Contribution Xu-jie Zhou from the Renal Division, Department of Medicine, Peking University First Hospital was awarded a fellowship from the academy od medical science, hosted by my team. We are studying together the role of the gut microbiome in IgAN risk, with microbiome experiments carried out in China and IgA glycomics in blood and gut carried out in Europe.
Collaborator Contribution Xu-jie Zhou from the Renal Division, Department of Medicine, Peking University First Hospital was awarded a fellowship from the academy od medical science, hosted by my team. We are studying together the role of the gut microbiome in IgAN risk, with microbiome experiments carried out in China and IgA glycomics in blood and gut carried out in Europe.
Impact A manuscript on GWAS of IgA glycans is under submission. PMID:33436510 has been published
Start Year 2021
 
Description UKCRN Portfolio Adoption 
Organisation UK Clinical Research Network (UKCRN)
Country United Kingdom 
Sector Charity/Non Profit 
PI Contribution A successful application was made to the North West London Ethics Committee to enable us to recruit patients with IgA Nephropathy on to our study. From these patients we collect samples to carry out research with. We are currently recruiting patients from the Imperial College Hospital NHS Trust (ICHNT), which is the host site and we have been adopted on to the UKCRN portfolio, which provides an infrastructure to support high quality clinical studies. We are also in the process of adding additional sites to our study, so patients can be recruited from other sites across the UK.
Collaborator Contribution The UKCRN provides an infrastructure to support high quality clinical studies, making the process of recruiting patients and processing the relevant documents easier, with an increased amount of support.
Impact With support from the UKCRN to date we have recruited 65 patients out of a target of 300.
Start Year 2014
 
Title PopPAnTe is a user-friendly platform-independent Java program that enables pairwise association testing of large number of predictors and response variables in related sample. 
Description Family-based designs, from twin studies to isolated populations with their complex genealogical data, are a valuable resource for genetic studies of heritable molecular biomarkers. Existing software for family-based studies have mainly focused on facilitating association between response phenotypes and genetic markers, and no user-friendly tools are at the present available to straightforwardly extend association studies in related samples to large datasets of generic quantitative data, as those generated by current -omics technologies. A manuscript describing the software is under review. This software is used for data integration of the IgAN project in familial settings. 
Type Of Technology Software 
Year Produced 2015 
Open Source License? Yes  
Impact No user-friendly tools are at the present available to straightforwardly extend association studies in related samples to large datasets of generic quantitative data, as those generated by current -omics technologies. The software is already used by several collaborators and is an important tool for the analysis of data generated for the IgAN project eg glycomics IgA data. 
URL http://www.twinsuk.ac.uk/project/poppante/
 
Title famCNV 
Description We extended our software famCNV. famCNV is now at version 2.1. This new version allows a more flexible input, and quantile normalisation can be automatically applied to each phenotype to improve normality of the response variables. Moreover, its output includes also beta and percentage of variance explained. The significance of the results is also now tested both through formal likelihood testing and through an empirical adaptive procedure. Version 2.0 is also more efficient in its implementation, allowing multithreading. The new version allows using both family data and unrelated subjects where the kinship matrix is estimated from the genetic data. We used famCNV to identify CNVs involved in IgAN using data previously generated in samples from the MRC/Kidney Research UK National DNA Bank for Glomerulonephritis, which are now under replication in an independent sample. 
Type Of Technology Software 
Year Produced 2015 
Open Source License? Yes  
Impact Raw intensity data from GWAS panels can be used to model association between CNV and phenotype using both family and independent samples. The new implementation 2.0 have been used to study the association between IgA and CNV in case control and family studies, and of the deglycosylated IgA. It has used also for additional projects (non IgAN) in our lab, including the identification of association between CNV at the AMY1 gene and obesity susceptibility. 
URL http://www.twinsuk.ac.uk/project/famCNV/
 
Description Recruiting Patients onto our study within ICHNT 
Form Of Engagement Activity Participation in an activity, workshop or similar
Part Of Official Scheme? No
Geographic Reach National
Primary Audience Patients, carers and/or patient groups
Results and Impact In order to recruit patients on to our study, the patients are first informed about the research we are doing. They are given an information sheet about the research and this sparks questions and discussion about the research. Often family members are with the patients so they are provided with information about the study too. Our study has 16 other NHS trusts also recruiting patients, so the discussion with patients, family and friends occurs at these sites too.

More people are aware of research being carried out on IgA Nephropathy
Year(s) Of Engagement Activity 2014,2015,2016