Prof. Steve Humphries

Research Lead

Professor Steve Humphries


Contact us

Rayne Building
5 University Street
London WC1E 6JF

Centre for Cardiovascular Genetics

The Centre for Cardiovascular Genetics - Section of Verhoeff Van Gieson stained brachocephalic arteries from following mice, after a 12 week    high fat diet,  to determine the extent of   atherosclerosis: ApoE-/-(ApoE), ApoE-/- fed elastase inhibitor(ApoE/EI) , ApoE-/- x human α-1-antitryp[sin transgenic mouse (ApoE/AAT) and wildtype C57/BL6 mice. (unpublished Dike and Talmud)


Over the past 20 years, work in the Centre for Cardiovascular Genetics (CVG) group has focused on genes coding for key proteins that are involved in lipid and lipoprotein metabolism, in the control of thrombosis and haemostasis, in maintaining vessel wall and plaque integrity, and energy utilisation, developed studies on genes that appeared promising and discarded those that did not. Our general approach has been based on the belief that a better understanding of the genetic components of coronary heart disease (CHD), and particularly of the underlying intermediate CHD phenotypes, will give novel insight into the pathological mechanisms of CHD that may lead to new therapeutic possibilities and may lead to the development of predictive tests for those at high risk. This aspect of our work has been successful as shown by several of our recent papers. The availability of the complete sequence of the human genome means that bioinformatics is playing an increasingly large part of the work that we do, and we are putting a considerable amount of effort into this aspect. In line with this we have funding from the BHF to carry out annotation of genes involved in cardiovascular processes using Gene Ontology.

Key research activities

Coronary Heart Disease

The field of CHD genetics has progressed at a phenomenal pace, driven by the technological advances of Genome Wide Association Scans (GWAS). The outcome from the GWAS has been to identify several new candidate genes, and the replication of their association with risk, the determination of risk in prospective studies, the analysis of gene-gene and gene-environmental interactions and the determination of the mechanisms of their functional role in CHD, is now a top priority. Our current major focus is to achieve this by carrying out specific genotyping and by having a significant role in the statistical analysis of the resulting data, to which end we have established the UCL, Edinburgh, Bristol Consortium of Genetic Studies (UCLEB). The aim of the consortium is to conduct research on a population scale that capitalises on the integration of genetic and non-genetic observational data using the 200K CV candidate genes chip, the Illumina Metabochip.

Cardiovascular disease

The strategies we use are based on the accepted view that CVD is a multifactorial disorder, with both environmental and genetic factors contributing. The identification of a specific causal mutation in a particular gene in a patient with early CVD (or more specifically a consistent difference in frequency of such a mutation between CVD cases and matched controls) demonstrates that the encoded protein in question is a key, rate-limiting step in the pathophysiological processes that underlie CVD. We are using many different molecular methods to prove causality of identified sequence variants in these CHD candidate genes. However, since CVD is multifactorial, any single mutation will at best be only making a small contribution to risk. To develop useful genetic tests will require the simultaneous study of several or many genes, and this programme of research is aimed at achieving this.

Familial Hypercholesterolaemia

Familial Hypercholesterolaemia (FH) continues to be a major part of our research activities. As one of the few monogenic cases of early CHD, FH is an ideal paradigm to develop methodologies for the application of genetic tests for CHD risk. FH is caused by mutations in the low density lipoprotein receptor gene (LDLR), the apolipoprotein B-100 gene (APOB) or the proprotein convertase subtilisin/kexin type 9 (PCSK9) genes. The most common genetic defect is a mutation in the LDLR gene. We have recently updated the UCL FH database, and currently over 1000 mutations have been reported world-wide, with >130 being reported in UK patients. Over the last 20 years we have developed and implemented molecular strategies to study the causes and clinical and psychological consequences of FH, and this work on mutation detection methods development continues. Prof Humphries co-directed the Department of Health funded UK-wide pilot for cascade testing of FH, was the Lead Clinical Advisor for the recently published NICE guidelines on FH, and is the project director for the RCP FH Audit.