Principal Investigator: Professor Hooman Allayee
University of Southern California, Los Angeles, California, USATags: 33307, biomarkers, cardiometabolic, genetics, risk scores, sex-stratified
Although cardiovascular disease (CVD) has traditionally been viewed as a disease of men, new evidence suggests the existence of distinct differences in the risk factors, development, and outcomes between the two sexes. For example, our recent studies have revealed that the genetic factors for several intermediate cardiometabolic traits, such as blood levels of certain amino acids (i.e. glycine) and lipids (i.e. ceramides), represent potentially novel sex-specific mechanisms for CVD. This project proposes to build on our observations using genetic and clinical cardiometabolic data from the UK Biobank.
By helping to determine the genetic basis of CVD, our proposed analyses could identify novel therapeutic targets and/or risk stratification tools. Thus, these studies would be consistent with UK Biobank’s stated purpose to improve the prevention, diagnosis and treatment of a wide range of illnesses, including heart diseases. The genotype and specific clinical data we request from all UK Biobank participants will be used for statistical analyses. These large-scale computations will specifically test for genetic associations in men and women separately. We will also carry out these sex-stratified tests with the genetic risk factors all combined together in what is typically referred to as `genetic risk score analysis.` Full cohort for genotypes and clinical binary and quantitative CVD traits.
Project extension – December 2019
We propose to expand the scope of our UK Biobank application by identifying gene-sex and gene-environment (GxE) interactions for CVD, obesity, and asthma-related traits and determine whether they are shared between these diseases. This is based on the literature and our own studies showing 1) the coexistence of these disease entities; 2) sex-specific association of genetic variants with CVD, obesity, and asthma-related traits; 3) and similarly adverse effects of environmental exposures, such as air pollution, on these diseases. We will carry out candidate gene and whole-genome analyses for CVD, obesity, and asthma-related traits in UK Biobank, followed by meta-analyses with publicly available data from other sources/consortia, including BioBank Japan, CARDIoGRAM+C4D (CVD), Trans-National Asthma Genetic Consortium (asthma), and GIANT/DIAGRAM (obesity/diabetes). In UK Biobank, we will also perform sex-stratified and gene-sex and gene-air pollution interaction analyses for CVD, obesity, and asthma-related traits. The results of these analyses will be compared to determine whether any identified genetic determinants and gene-sex or gene-air pollution interactions are shared across diseases. In addition to individual variants, we will also evaluate association of risk alleles, through either main effects or interactions, as a function of cumulative genetic burden through the construction of polygenic and genetic risk scores.
Last updated Dec 18, 2019