45 genes reveal new molecular associations with obesity
Updated: Jan 23
Researchers from the Department of Biomedical Informatics (DBMI) at the University of Colorado School of Medicine have identified 45 genes whose gene expression is associated with body mass index (BMI), many of which have not been previously explored in obesity research, after the researchers conducted a study using a multi-ethnic cohort. Their study, ‘Gene Expression Associations With Body Mass Index in the Multi-Ethnic Study of Atherosclerosis’, published in the International Journal of Obesity, points to potential new biomarkers for obesity. The team accomplished this by tapping into data from a large, diverse cohort that was originally gathered in 2000.
"Until now, few genetic studies of BMI have been conducted in ancestrally diverse cohorts," explained lead author, Luciana Vargas, a CU School of Medicine PhD student, who said these known and novel gene associations can provide insights into the biology of obesity, potential biomarkers and therapeutic targets. "The novelty of our study is the use of directly measured gene expression data."
For their study, researchers in the DBMI labs of Drs Ethan Lange and Leslie Lange, leveraged data from the Multi-Ethnic Study of Atherosclerosis (MESA). When it was launched, MESA enrolled over 6,000 people, recruited from six field centres across the US, to research risk factors and the early characteristics of cardiovascular disease. Participants continue to report to field centres periodically for collection of health data.
Because of the large, ethnically diverse study population, and the amount of health information collected, researchers have used its data for a multitude of studies. The Trans-Omics for Precision Medicine (TOPMed) consortium, which launched in 2014, began gathering gene expression and other omics data on a subset of MESA participants, as well as participants from many other cohorts.
"We used the MESA cohort because it's really difficult to find a well-defined cohort with a lot of good clinical measurements, get the funding, and maintain the contact with study participants to collect blood and do these studies over time," added Dr Iain Konigsberg, a biomedical informatics research instructor who works with Vargas in the DBMI Lange Lab.
The researchers analysed RNA sequencing data from four self-identified race and ethnic groups in the MESA cohort - African American, Chinese American, Hispanic and white - to assess the association of expression of each gene for an effect on BMI. Many of the characteristics related to cardiovascular risk are also relevant to obesity, making the MESA cohort ideal for obesity research.
Across all groups, 45 genes were identified by meta-analysis whose expression was significantly associated with BMI, explaining 29.7% of BMI variation. The 45 genes are expressed in a variety of tissues and cell types and are enriched for obesity-related processes including erythrocyte function, oxygen binding and transport, and JAK-STAT signalling. While a small number of these genes have been identified through genetic association studies, the CU authors reported many novel associations.
Konigsberg explained their work points to the need for more diversity in obesity research and expects the results of this study to inform additional downstream studies. He expects to continue research using MESA and additional human cohorts.