title: DRD2: Bridging the Genome and Ingestive Behavior.
abstract: Recent work highlights the importance of genetic variants that influence brain structure and function in conferring risk for polygenic obesity. The neurotransmitter dopamine (DA) has a pivotal role in energy balance by integrating metabolic signals with circuits supporting cognitive, perceptual, and appetitive functions that guide feeding. It has also been established that diet and obesity alter DA signaling, leading to compulsive-like feeding and neurocognitive impairments. This raises the possibility that genetic variants that influence DA signaling and adaptation confer risk for overeating and cognitive decline. Here, we consider the role of two common gene variants, FTO and TaqIA rs1800497 in driving gene × environment interactions promoting obesity, metabolic dysfunction, and cognitive change via their influence on DA receptor subtype 2 (DRD2) signaling.
authors.affiliation: Department of Psychology, University of Pennsylvania, Philadelphia, PA, USA.
authors.forename: Xue
authors.initials: X
authors.lastname: Sun
authors.affiliation: Université Paris Diderot, Sorbonne Paris Cité, BFA CNRS UMR 8251, Paris, France; Modern Diet and Physiology Research Center, New Haven, CT, USA.
authors.forename: Serge
authors.initials: S
authors.lastname: Luquet
authors.affiliation: Modern Diet and Physiology Research Center, New Haven, CT, USA; The John B. Pierce Laboratory, 290 Congress Avenue, New Haven, CT, USA; Department of Psychiatry, Yale School of Medicine, New Haven, CT, USA; Department of Psychology, Yale University, New Haven, CT, USA. Electronic address: dana.small@yale.edu.
authors.forename: Dana M
authors.initials: DM
authors.lastname: Small
mesh_terms: D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO / Q000235:genetics*; D004298:Dopamine; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease; D006801:Humans; D009765:Obesity / Q000235:genetics*; D017346:Protein Serine-Threonine Kinases / Q000235:genetics*; D017448:Receptors, Dopamine D2 / Q000235:genetics*
chemical_list: C581293:DRD2 protein, human; D017448:Receptors, Dopamine D2; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human; D017346:Protein Serine-Threonine Kinases; D004298:Dopamine
keywords: ANKK1; cognition; diet; dopamine; genetics; inflammation; ingestive behavior; obesity