title: Personality as an intermediate phenotype for genetic dissection of alcohol use disorder.
abstract: Genetic and environmental interactive influences on predisposition to develop alcohol use disorder (AUD) account for the high heterogeneity among AUD patients and make research on the risk and resiliency factors complicated. Several attempts have been made to identify the genetic basis of AUD; however, only few genetic polymorphisms have consistently been associated with AUD. Intermediate phenotypes are expected to be in-between proxies of basic neuronal biological processes and nosological symptoms of AUD. Personality is likely to be a top candidate intermediate phenotype for the dissection of the genetic underpinnings of different subtypes of AUD. To date, 38 studies have investigated personality traits, commonly assessed by the Cloninger's Tridimensional Personality Questionnaire (TPQ) or Temperament and Character Inventory (TCI), in relation to polymorphisms of candidate genes of neurotransmitter systems in alcohol-dependent patients. Particular attention has been given to the functional polymorphism of the serotonin transporter gene (5-HTTLPR), however, leading to contradictory results, whereas results with polymorphisms in other candidate monoaminergic genes (e.g., tryptophan hydroxylase, serotonin receptors, monoamine oxidases, dopamine receptors and transporter) are sparse. Only one genome-wide association study has been performed so far and identified the ABLIM1 gene of relevance for novelty seeking, harm avoidance and reward dependence in alcohol-dependent patients. Studies investigating genetic factors together with personality could help to define more homogenous subgroups of AUD patients and facilitate treatment strategies. This review also urges the scientific community to combine genetic data with psychobiological and environmental data to further dissect the link between personality and AUD.
authors.affiliation: Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Lars
authors.initials: L
authors.lastname: Oreland
authors.affiliation: Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Gianvito
authors.initials: G
authors.lastname: Lagravinese
authors.affiliation: Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden.
authors.forename: Simone
authors.initials: S
authors.lastname: Toffoletto
authors.affiliation: Centre for Clinical Research, Uppsala University, Västmanland County Counci, Västerås, Sweden.
authors.forename: Kent W
authors.initials: KW
authors.lastname: Nilsson
authors.affiliation: Division of Neuropsychopharmacology, Department of Psychology, University of Tartu, Tartu, Estonia.|Psychiatry Clinic, North Estonia Medical Centre, Tallinn, Estonia.
authors.forename: Jaanus
authors.initials: J
authors.lastname: Harro
authors.affiliation: Department of Psychiatry, School of Medicine, Washington University, St. Louis, MO, USA.
authors.forename: C
authors.initials: C
authors.lastname: Robert Cloninger
authors.affiliation: Department of Neuroscience, Uppsala University, BMC, Box 593, 751 24, Uppsala, Sweden. erika.comasco@neuro.uu.se.
authors.forename: Erika
authors.identifier: 0000-0002-2174-2068
authors.initials: E
authors.lastname: Comasco
mesh_terms: D000437:Alcoholism / Q000235:genetics*; D005260:Female; D059647:Gene-Environment Interaction; D005819:Genetic Markers / Q000235:genetics*; D055106:Genome-Wide Association Study / Q000379:methods; D006801:Humans; D060588:LIM Domain Proteins / Q000235:genetics; D008297:Male; D008840:Microfilament Proteins / Q000235:genetics; D010551:Personality / Q000235:genetics*; D010641:Phenotype; D050486:Serotonin Plasma Membrane Transport Proteins / Q000235:genetics
chemical_list: C107440:ABLIM1 protein, human; D005819:Genetic Markers; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D050486:Serotonin Plasma Membrane Transport Proteins
keywords: AUD; Alcohol; Gene; Personality; Serotonin