Principal Investigator: Dr Lu Qi
Tulane University, Epidemiology, 1440 Canal Street, Suite 1724, New Orleans LA 70112, United StatesTags: 29256, cardiometabolic risk, GxE, MR, obesity
1a: Obesity and cardiometabolic risk are the major threats to the public health worldwide, determined by genetic susceptibility, environmental risk factors, and their interactions; however, it is still a lack of evidence of G×E interaction and unconfounded estimates of a modifiable exposure. This project is expected to ⑴ examine whether diet, lifestyles, and early life exposures may interact with the genetic variations in relation to obesity and cardiometabolic risk, and to ⑵test the causal effect of a modifiable exposure on the outcomes (e.g. hypertension, insulin resistance, dyslipidemia, type 2 diabetes) using Mendelian randomization analysis.
1b: Sufficient sample size in UK Biobank and its extensive information on diet, lifestyle, early life factors, and genetics enable us to explore G×E interaction and causality of different risk factors in the pathogenic mechanisms underlying obesity and cardiometabolic disorders. The findings will eventually contribute to the improvement of the prevention, diagnosis, and treatment of common complex diseases.
1c: In the G×E interaction analysis, we will create different types of genetic predisposition scores for each participant, and examine whether early life, diet, and lifestyle risk factors may interact with the genetic scores in relation to obesity and major cardiometabolic disorders. As for Mendelian randomization (MR) analyses, genetic proxy markers for well-understood effects on modifiable exposures will be used to evaluate the causal effects on the outcome.
1d: We plan to use the full cohort.
Project extension – January 2020
Obesity, cardiometabolic risk, as well as aging-related disorders (such as healthy aging, cognitive function, frailty, sarcopenia, and osteoporosis) have been major public health burdens worldwide. These disease conditions might be determined by genetic susceptibility, environmental risk factors, and their interactions; however, scarce evidence exists on gene-environment interactions and unconfounded estimates of modifiable exposures in a large cohort. This project is expected to examine whether environmental risk factors (such as diet, lifestyles, environmental factors, and early life exposures) may interact with genetic variations in relation to outcomes of cardiometabolic and aging-related diseases (such as obesity and related morbidities, major adverse cardiovascular events and death, and other aging-related conditions). This project also considers known risk factors of the above outcomes (e.g. hypertension, insulin resistance, dyslipidemia, type 2 diabetes, drinking, smoking, sleeping, brain structure) and subclinical changes (e.g. imaging changes and biomarkers). We will also test the causal effect of an exposure of interest on our study outcomes and their risk factors using Mendelian randomization analysis.
Last updated Feb 7, 2020