Omics, Obesity, and Cardiometabolic Diseases

We are very interested in the molecular signals linking obesity with cardiometabolic diseases.  A key interest is in examining the well-known demands of obesity on metabolism, thereby affecting cardiometabolic diseases. We are studying the microbiome and metabolome in China. In CARDIA, we are using longitudinal metabolomics data to ask questions about metabolic disturbances in relation to cardiometabolic diseases.  We are particularly interested in the evolution of CVD in the context of unremitting metabolic stress induced by obesity and CVD risk factors. In Add Health we are examining exome data to identify variants that underlie weight gain in the transition to obesity and we are interested in the interplay between genetics and environmental factors.

Transition to a Western Diet and Cardiometabolic Risk: Biomarkers Derived from the Microbiome (R01DK104371). National Institutes of Health, National Institute of Diabetes and Digestive and Kidney Diseases. Principal Investigator: Penny Gordon-Larsen. 9/01/2015-6/30/2021.

China is a rapidly modernizing country experiencing substantial transition from traditional to Westernized diet at different points in time, and across diverse geographic regions, along with increasing burden of obesity, diabetes and inflammation, providing a unique model for examining development of risk. This project investigates how long-term and short-term changes in diet, gut microbiota, gut microbiota-related plasma metabolites and microbiota-influenced markers of cardiometabolic disease interrelate in order to inform efforts to mitigate early development of disease risk across the globe.

Leveraging multi-omics approaches to examine metabolic challenges of obesity in relation to cardiovascular diseases (R01HL143885). National Institutes of Health, National Heart, Lung, and Blood Institute. Principal Investigator: Penny Gordon-Larsen. 4/01/2019 – 3/31/2023.

There is limited understanding of the molecular mechanisms leading to cardiovascular disease (CVD), particularly in the context of obesity. Our studies aim to use genomics and metabolomics data to reveal mechanisms important in CVD, with strong potential for identifying biomarkers of CVD risk. Ultimately, this mechanistic framework will help identify novel therapeutic and nutritional targets to reduce the global burden of CVD.

Exome Variants Underlying Weight Gain from Adolescence to Adulthood (1R01HD057194). Competing Continuation. National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. Principal Investigator: Penny Gordon-Larsen. 4/01/2014-6/30/2021.

The objective of the research is to investigate how genetic variation influences weight-related traits during the transition from adolescence to adulthood – a critical risk period for weight gain. This is an area where there has not been sufficient research to understand how individual susceptibility to environmental contexts influences attained size and trajectories of body mass change. We build on our successes in R01HD057194 and capitalize on nationally representative, ethnically diverse, prospective and well-characterized data on 10,581 individuals from the National Longitudinal Study of Adolescent to Adult Health (Add Health) to assess the association between weight-related traits and coding variants across a 15-year lifecycle period of dramatic weight gain between adolescence and adulthood. In addition, we are collaborating with researchers from the Cohorts for Heart and Aging Research in Genomic Epidemiology consortium (CHARGE), the China Health and Nutrition Survey (CHNS), and the Cebu Longitudinal Health and Nutrition Survey (CLHNS) living under different environmental conditions but experiencing high levels of weight gain analogous to Add Health.

We have a wonderful team of UNC researchers, including Drs. Kari North, Ethan Lange, Karen Mohlke, Annie Green Howard, Leslie Lange, Misa Graff, Kristin Young, Ken Bollen, and Kathie Mullan Harris).

The original project was:

Gene-Environment Interactions and Weight Gain (R01HD057194). National Institutes of Health, Eunice Kennedy Shriver National Institute of Child Health and Human Development. Principal Investigator: Penny Gordon-Larsen. 09/30/2008-6/30/2013.

The objective of this research project was to investigate how genes, environment, and gene-environment interactions influence temporal changes in body mass index (BMI) at vulnerable periods of the life cycle. This is an area where there has not been sufficient research to understand how individual susceptibility to environmental contexts influences attained size and trajectories of body mass change. In this study, we used data from The National Longitudinal Study of Adolescent Health (Add Health)  to investigate how the effects of genetic variation are modified by the environment. We were particularly interested in identifying genetic loci influencing weight gain during the transition from late adolescence and early adulthood and how effects of these genes vary across European American, African American, Hispanic, and Asian American individuals. We were also investigating environmental factors that might predispose individuals to weight gain. Once we have a better understanding of the separate influence of genetic and environmental factors, we will move to gene by environment interactions to form a better understanding of interactions between genetic variation and modifiable environmental factors in the determination of weight gain.

Penny Gordon-Larsen has been working with the Add Health study for almost 15 years and has published widely with this wonderful dataset. The genetic data that we will develop as part of this project is able to be linked with a database that Gordon-Larsen and her team has developed for Add Health, called the Obesity & Neighborhood Environment database (ONEdata)