Identification of pleiotropic genetic effects on obesity and brain anatomy

Authors

Joanne E. Curran, The University of Texas Rio Grande Valley
D Reese McKay
Anderson M. Winkler, The University of Texas Rio Grande ValleyFollow
Rene L. Olvera
Thomas D. Dyer, The University of Texas Rio Grande Valley
Peter T. Fox
Laura Almasy
Ravi Duggirala, The University of Texas Rio Grande Valley
John Blangero, The University of Texas Rio Grande Valley
David C. Glahn

Document Type

Article

Publication Date

1-1-2013

Abstract

Background/aims: Obesity is a major contributor to the global burden of chronic disease and disability, though current knowledge of causal biologic underpinnings is lacking. Through the regulation of energy homeostasis and interactions with adiposity and gut signals, the brain is thought to play a significant role in the development of this disorder. While neuroanatomical variation has been associated with obesity, it is unclear if this relationship is influenced by common genetic mechanisms. In this study, we sought genetic components that influence both brain anatomy and body mass index (BMI) to provide further insight into the role of the brain in energy homeostasis and obesity.

Methods: MRI images of brain anatomy were acquired in 839 Mexican American individuals from large extended pedigrees. Bivariate linkage and quantitative analyses were performed in SOLAR.

Results: Genetic factors associated with an increased BMI were also associated with a reduced cortical surface area and subcortical volume. We identified two genome-wide quantitative trait loci that influenced BMI and the ventral diencephalon volume, and BMI and the supramarginal gyrus surface area, respectively.

Conclusions: This study represents the first genetic analysis seeking evidence of pleiotropic effects acting on both brain anatomy and BMI. Our results suggest that a region on chromosome 17 contributes to the development of obesity, potentially through leptin-induced signaling in the hypothalamus, and that a region on chromosome 3 appears to jointly influence the food-related reward circuitry and the supramarginal gyrus.

Comments

© 2013 S. Karger AG, Basel.

Recommended Citation

Curran, J. E., McKay, D. R., Winkler, A. M., Olvera, R. L., Carless, M. A., Dyer, T. D., Kent, J. W., Jr, Kochunov, P., Sprooten, E., Knowles, E. E., Comuzzie, A. G., Fox, P. T., Almasy, L., Duggirala, R., Blangero, J., & Glahn, D. C. (2013). Identification of pleiotropic genetic effects on obesity and brain anatomy. Human heredity, 75(2-4), 136–143. https://doi.org/10.1159/000353953

First Page

136

Last Page

43

Publication Title

Human heredity

DOI

10.1159/000353953

Academic Level

faculty

Mentor/PI Department

Office of Human Genetics