Our research focuses on the application of large-scale genomic analysis to unravel the spectrum of human genetic variation associated with cardiometabolic diseases, and its interaction with non-genetic and environmental cues.

Common, complex conditions such as cardiovascular, inflammatory and immune diseases can be considered as extremes of a broad spectrum of phenotypic variation that is also seen in healthy individuals. Our group is interested in understanding how genetic factors interact with other non-genetic and so-called epigenetic factors to determine such phenotypic variation. To achieve this, we use large-scale genome scans including genome sequencing data, epigenetic profiling and molecular traits such as gene expression and metabolomics. We strongly believe in the value of data sharing. We have generated rich genomic datasets for the scientific community, including an expansive atlas of genetic associations with metabolites, whole-genome sequence and phenotype data for population cohorts in the UK10K project, as well as bioinformatic resources to facilitate the retrieval of information, including a metabolite network, a database of genotype-metabolite associations with our colleagues at the HelmHoltz institute, and a genome browser of UK10K association results.

Core team

Photo of Klaudia Walter

Klaudia Walter

Senior Staff Scientist

Photo of Stephen Watt

Stephen Watt

Senior Staff Scientist

Previous core team members

Photo of Dr Anna Cuomo

Dr Anna Cuomo

Research Associate

Photo of Dr Heather Elding

Dr Heather Elding

Postdoctoral Fellow

Photo of Dr Valentina Iotchkova

Dr Valentina Iotchkova

EBI Sanger Postdoctoral Fellow

Photo of Kousik Kundu

Kousik Kundu

Postdoctoral Fellow

Photo of Paris Litterick

Paris Litterick

Team Administrator

Photo of Dr Alice Mann

Dr Alice Mann

Head of Academic Programmes

Photo of Dr Hannes Ponstingl

Dr Hannes Ponstingl

Principal Bioinformatician

Photo of Louella Judy Vasquez

Louella Judy Vasquez

Staff Scientist

Photo of Dragana Vuckovic

Dragana Vuckovic

Postdoctoral Fellow

Photo of Dr Ying Yan

Dr Ying Yan

Former Senior Bioinformatician at the Sanger Institute

Partners

We work with the following groups

External

BLUEPRINT

As an extension to genetics projects, we now aim to identify and characterize in greater depth genes implicated in hematopoietic development in the EU FP7-funded BLUEPRINT project, which will generate reference genomes and epigenomes of at least 100 specific blood cell types. Our group coordinates the EpiVar package of the BLUEPRINT project, which is generating genomic (through whole-genome sequencing) and epigenetic characterization of three main immune cell types in 200 individuals, with the aim characterize the role of human variation on the epigenomic landscape.

External

EpiGeneSys

This Epigenesys-funded project aims to apply system genetic approaches based on Bayesian networks to model regulatory pathways between genetic variants and molecular phenotypes measured in blood cells. Specifically, the project will seek to characterize genetic variants regulating the processes of differentiation, proliferation and fate determination in the human haematopoietic system. Such analyses will be based on novel genomic, transcriptomic and epigenetic datasets generated for all mature blood cell types and their precursors by the EU-funded BLUEPRINT project. Furthermore, through collaboration with Dr Cedric Ghevaert and Dr Ludovic Vallier at the University of Cambridge, we will seek to extend analyses to select blood cells derived from human induced pluripotent stem cells. Dr Louella Vasquez (PhD Physics, WTSI Postdoctoral Fellow) is responsible for the statistical analyses and development of new modeling approaches.

External

CTTV metabolomics

We are extending the previous metabolomics genetics approaches to drug development applications with different aims. The first is looking at other associations to the same metabolite as potential additional loci involved in the disease process. The second is understanding of potential causal pathways involving these metabolites. The third is the development of metabolite measurements as useful biomarkers / alternative end points.

External

NIHR BTRU in Donor Health and Genomics

We are part on the newly launched NIHR Blood and Transplant Research Unit in Donor Health and Genomics, where we coordinate theme 1 - Determinants of donation-related biomarkers.This theme will address the NIHR BTRU mandate to identify and characterise “genetic, biochemical, lifestyle and other determinants of relevant blood cell traits…and measures of iron homeostasis, including determinants of the trajectories of these factors over time among donors”.The rationale is that such information is needed to understand molecular and health consequences of repeated donation. Through analysis of the INTERVAL Trial data, serial follow-up of donors and mechanistic studies, Theme 1 will help identify people who can give blood more (or less) frequently than is typical, feeding into Themes 2-3 by identifying “genomic and other factors associated with capacity to give blood”, informing “evidence-based strategies to prevent deferral”.

 

Publications

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