Approved research

Gene-Lifestyle interactions in cardiometabolic disease traits

Lay summary

Despite great success, much of the genetic component remains unknown for high blood pressure (BP) and unfavorable levels of plasma lipids which are important risk factors for cardiovascular diseases. Gene-Lifestyle (GxL) interactions, relevant to underlying pathobiology, offer an exciting opportunity for discovering large numbers of new loci. UK Biobank is well-powered for such analyses. The aims are a) identify novel genetic loci and to characterize interactions in known loci, b) perform an expanded GxL meta-analysis including studies already in the NHLBI funded CHARGE GxL Interactions project (>800,000 individuals), c) create genetic and lifestyle risk scores for predicting cardiovascular outcomes. UK Biobank aims to improve the diagnosis, treatment, and prevention of a wide range of serious and life-threatening illnesses. To provide a better understanding of the genetic regulation of BP and lipid levels we will perform GxL interaction analyses for these traits using the lifestyle factors (smoking, alcohol intake, physical activity, sleep, education, diet and psychosocial). The aim of these analyses is to identify additional novel genetic loci, provide new insights into biological mechanisms regulating BP and lipid levels, and investigate their usefulness and relevance for predicting clinical outcomes and to identify new targets for therapeutic innovation. High BP and unfavorable levels of plasma lipids are both important risk factors for cardiovascular diseases. Together, they constitute a major public health burden. GxL interactions play an important role in the pathobiology of disease traits, and offer an exciting opportunity to enhance our understanding about which combinations of genes and lifestyle factors predispose to unfavourable outcomes. We will perform GxL interaction analyses across a range of pre-defined lifestyle factors to identify novel genes, and create genetic and lifestyle risk scores to see if we can better predict cardiovascular outcomes. We request data from the full cohort. Analyses are currently underway in the CHARGE Gene-Lifestyle Interactions Working Group for six lifestyle domains (smoking, alcohol consumption, education, physical activity, psychosocial, and sleep) in approx. 130,000 individuals, with replication in >300,000 individuals. Results from some of these projects are expected later in 2016. The release of genetic data from the full cohort later this year is synergistic with our timeline to initiate an enlarged GxL meta-analyses with an increased number of lifestyle variables. Immediate access to the subset of ~150,000 with genetic data will help validate some of the current discoveries.