A Multi-Ancestry Study of Gene-Lifestyle Interactions and Multi-Omics in Cardiometabolic Traits (Gene-lifestyle interactions Phase II – CHARGE consortium)
In 2014, we established the CHARGE Consortium’s Gene-Lifestyle Interactions Working Group (WG) and a robust infrastructure including an Analysis Committee. We launched a multi-ancestry (European, African, Hispanic, and Asian) collaborative study to investigate the role of gene-lifestyle interactions in the pathophysiology of cardiovascular disease (including blood pressure (BP) and lipids), constituting our Phase I activities (Rao et al., PMID:28620071).
Some of the Phase I studies participated as part of “discovery” and performed genome-wide interaction analyses (GWIS). Others participated as part of “replication”. Robust GWIS analysis pipelines were established in all participating studies. Phase I investigations identified several genes for BP and lipid traits with biological plausibility. Although interactions (GxE) contributed to varying degrees in identifying these genes, post-hoc analysis found that our sample size for GWIS in stage 1 (~130K) had limited statistical power.
Building on the already established collaborations with an outstanding team of investigators, we are now launching a substantially expanded Phase II investigation to assess the potential impact and translational value of GWIS for cardiometabolic traits and important clinical endpoints (coronary heart disease [CHD], stroke, and type 2 diabetes [T2D]). We are expanding the GWIS sample size by at least 10-fold, yielding much greater power to identify interactions. Early Phase II Analysis Plans are in advanced stages of preparation. Unlike in Phase I, all studies participating in Phase II will undertake full GWIS. Subsequently, focused analysis of longitudinal data will be pursued, as well as the role of interactions in clinical endpoints through genetic risk scores. All participating studies will have authorship opportunities on resulting publications. Opportunities exist for you to lead one or more projects.
We are writing now to invite your participation in our Phase II projects. Some of you are already participating in Phase I GWIS projects; some of you are participating in ICBP GWAS activities; while others may have the needed data and are willing to participate in collaborative analysis and multi-author publications. You may receive this invitation multiple times if you are a PI/Leader of multiple studies. If you have data on any of the cardiometabolic traits and at least one of the lifestyle traits listed below, we hope that you will consider participating.
Phenotypic domains targeted: (One or more of): Blood Pressure (BP), Lipids, Adiposity, and Diabetes traits.
Lifestyle domains targeted: (One or more of): Smoking, Alcohol consumption, physical activity, educational attainment, psychosocial factors, and sleep duration
DC Rao, CHARGE Gene-Lifestyle Interactions Working Group
Patricia Munroe, ICBP