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.
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.
Authors: A H Kissebah; G E Sonnenberg; J Myklebust; M Goldstein; K Broman; R G James; J A Marks; G R Krakower; H J Jacob; J Weber; L Martin; J Blangero; A G Comuzzie Journal: Proc Natl Acad Sci U S A Date: 2000-12-19 Impact factor: 11.205
Authors: Cyrus A Raji; April J Ho; Neelroop N Parikshak; James T Becker; Oscar L Lopez; Lewis H Kuller; Xue Hua; Alex D Leow; Arthur W Toga; Paul M Thompson Journal: Hum Brain Mapp Date: 2010-03 Impact factor: 5.038
Authors: B D Mitchell; C M Kammerer; J Blangero; M C Mahaney; D L Rainwater; B Dyke; J E Hixson; R D Henkel; R M Sharp; A G Comuzzie; J L VandeBerg; M P Stern; J W MacCluer Journal: Circulation Date: 1996-11-01 Impact factor: 29.690
Authors: David C Glahn; Joanne E Curran; Anderson M Winkler; Melanie A Carless; Jack W Kent; Jac C Charlesworth; Matthew P Johnson; Harald H H Göring; Shelley A Cole; Thomas D Dyer; Eric K Moses; Rene L Olvera; Peter Kochunov; Ravi Duggirala; Peter T Fox; Laura Almasy; John Blangero Journal: Biol Psychiatry Date: 2011-10-07 Impact factor: 13.382
Authors: R Duggirala; J Blangero; L Almasy; T D Dyer; K L Williams; R J Leach; P O'Connell; M P Stern Journal: Am J Hum Genet Date: 1999-04 Impact factor: 11.025
Authors: Shahram Bahrami; Nils Eiel Steen; Alexey Shadrin; Kevin O'Connell; Oleksandr Frei; Francesco Bettella; Katrine V Wirgenes; Florian Krull; Chun C Fan; Anders M Dale; Olav B Smeland; Srdjan Djurovic; Ole A Andreassen Journal: JAMA Psychiatry Date: 2020-05-01 Impact factor: 21.596
Authors: Jessica L Joganic; Katherine E Willmore; Joan T Richtsmeier; Kenneth M Weiss; Michael C Mahaney; Jeffrey Rogers; James M Cheverud Journal: Am J Phys Anthropol Date: 2017-11-20 Impact factor: 2.868
Authors: Rene L Olvera; Douglas E Williamson; Susan P Fisher-Hoch; Kristina P Vatcheva; Joseph B McCormick Journal: J Clin Psychiatry Date: 2015-10 Impact factor: 4.384
Authors: Erika J Wolf; Danielle R Miller; Mark W Logue; Jennifer Sumner; Tawni B Stoop; Elizabeth C Leritz; Jasmeet P Hayes; Annjanette Stone; Steven A Schichman; Regina E McGlinchey; William P Milberg; Mark W Miller Journal: Brain Behav Immun Date: 2017-06-01 Impact factor: 7.217
Authors: Emma Sprooten; Cota Navin Gupta; Emma E M Knowles; D Reese McKay; Samuel R Mathias; Joanne E Curran; Jack W Kent; Melanie A Carless; Marcio A Almeida; Thomas D Dyer; Harald H H Göring; Rene L Olvera; Peter Kochunov; Peter T Fox; Ravi Duggirala; Laura Almasy; Vince D Calhoun; John Blangero; Jessica A Turner; David C Glahn Journal: Am J Med Genet B Neuropsychiatr Genet Date: 2015-10-05 Impact factor: 3.568