Close
Members
Tom Lumbers MA MRCP, PhD, Clinical Lecturer
Daniel Swerdlow MRCP, PhD, Clinical
Lecturer
Sonia Shah, PhD, Senior Research
Associate
Ghazelah Fatimefar, PhD, Research Associate
Albert Henry, MSc, Research Assistant
Funding
MRC UK, NIHR, American Heart Association, Pfizer, Bayer.
Location
UCL Farr Institute, 222 Euston Road, NW1 2DA
Overview
Heart failure places
a substantial burden on population health and better understanding of causal
human biology is needed to enable development of effective therapeutic
approaches, which are currently lacking. Pre-clinical disease models have
proved poorly predictive of human disease and the therapeutic pipeline for
heart failure is limited. Our research seeks
to use large-scale genetic studies and integrative –omic approaches to advance
the understanding of disease mechanisms in heart failure and related
sub-phenotypes. The group pursues these aims through collaboration, serving the
HERMES consortium (below) as lead
coordinating centre, providing operational and analytic support.
At UCL, we work closely with colleagues at the Institute of Health Informatics, to refine heart failure phenotypes at scale using genomic enriched electronic health records (denaxaslab.org), and with the Population Genomics and Drug Development Group (link).
The specific objectives are:
1. To identify genetic variants influencing risk and prognosis in heart failure and related sub-phenotypes through large-scale genome-wide association meta-analysis and fine-mapping;
2. To investigate functional mechanisms linking heart failure loci to disease outcomes through fine-mapping, functional annotation and integrative analyses with GWA data from related disease and biomarker traits;
3. To use Mendelian randomisation to test existing disease hypotheses, including the causal role of established risk factors and the efficacy and safety of putative drug targets.
Key achievements
- Completed collaborative GWAS meta-analysis of >30, 000 HF cases and >200,000 controls, across 27 studies and identified a number of risk loci, implicating novel genes in heart failure risk.
- Large scale meta-analyses of stratified subsets and longitudinal phenotypes underway.
Collaborations
Prof Aroon Hingorani, University College
London
Ass. Prof Spiros
Denaxas, University
College London
Prof Vasan
Ramachandran, Boston
University
Prof Naveed Sattar, Glasgow University
Dr Tom Cappola, University of
Pennsylvania
Prof Chim Lang, University of
Dundee
Dr Anders Malarstig, Karolinska Institute
HERMES (HEart FailuRe Molecular Epidemiology
for therapeutic targetS)