title: A DRD4 gene by maternal sensitivity interaction predicts risk for overweight or obesity in two independent cohorts of preschool children.
abstract: Recent evidence suggests that early exposure to low maternal sensitivity is a risk factor for obesity in children and adolescents. A separate line of study shows that the seven-repeat (7R) allele of the dopamine-4 receptor gene (DRD4) increases susceptibility to environmental factors including maternal sensitivity. The current study integrates these lines of work by examining whether preschoolers carrying the 7R allele are more vulnerable to low maternal sensitivity as it relates to overweight/obesity risk.
  
  
  
  The Maternal Adversity Vulnerability and Neurodevelopment (MAVAN) project in Canada was used as the discovery cohort (N = 203), while the Generation R study in the Netherlands was used as a replication sample (N = 270). Regression models to predict both continuous BMI z-scores and membership in any higher BMI category based on established World Health Organization (WHO) cutoffs for 48 months of age were completed.
  
  
  
  In both cohorts, there was a significant maternal sensitivity by DRD4 by sex interaction predicting higher body mass indices and/or obesity risk. As hypothesized, post hoc testing revealed an inverse relationship between maternal sensitivity and body mass indices in 7R allele carriers relative to noncarriers. This finding was strongest in girls in the Canadian cohort and in boys in the Dutch cohort.
  
  
  
  Many children who carry the 7R allele of DRD4 appear to be more influenced by maternal sensitivity as it relates to overweight/obesity risk, consistent with a plasticity effect. Given the relatively small sample sizes available for these analyses, further replications will be needed to confirm and extend these results.
authors.affiliation: Centre for Addition and Mental Health (CAMH), Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: Robert D
authors.initials: RD
authors.lastname: Levitan
authors.affiliation: Institute of Psychology, Erasmus University Rotterdam, Rotterdam, Netherlands.|Departments of Child and Adolescent Psychiatry and Psychology, and Epidemiology, and Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Pauline
authors.initials: P
authors.lastname: Jansen
authors.affiliation: Institute of Medical Science, University of Toronto, Toronto, ON, Canada.
authors.forename: Barbara
authors.initials: B
authors.lastname: Wendland
authors.affiliation: Departments of Child and Adolescent Psychiatry and Psychology, and Epidemiology, and Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Henning
authors.initials: H
authors.lastname: Tiemeier
authors.affiliation: Departments of Child and Adolescent Psychiatry and Psychology, and Epidemiology, and Psychiatry, Erasmus University Medical Center, Rotterdam, The Netherlands.
authors.forename: Vincent W
authors.initials: VW
authors.lastname: Jaddoe
authors.affiliation: Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.
authors.forename: Patricia P
authors.initials: PP
authors.lastname: Silveira
authors.affiliation: Centre for Addition and Mental Health (CAMH), Toronto, ON, Canada.|Department of Psychiatry, University of Toronto, Toronto, ON, Canada.|Department of Physiology, University of Toronto, Toronto, ON, Canada.
authors.forename: James L
authors.initials: JL
authors.lastname: Kennedy
authors.affiliation: Ryerson University, Toronto, ON, Canada.
authors.forename: Leslie
authors.initials: L
authors.lastname: Atkinson
authors.affiliation: Department of Psychology, University of Toronto Mississauga, Mississauga, ON, Canada.
authors.forename: Alison
authors.initials: A
authors.lastname: Fleming
authors.affiliation: Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, ON, Canada.
authors.forename: Marla
authors.initials: M
authors.lastname: Sokolowski
authors.affiliation: Department of Psychiatry and Neurology, McGill University, Montreal, QC, Canada.
authors.forename: Helene
authors.initials: H
authors.lastname: Gaudreau
authors.affiliation: McMaster University, Hamilton, ON, Canada.
authors.forename: Meir
authors.initials: M
authors.lastname: Steiner
authors.affiliation: Department of Management, McGill University, Montreal, QC, Canada.
authors.forename: Laurette
authors.initials: L
authors.lastname: Dubé
authors.affiliation: Hospital for Sick Children, Toronto, ON, Canada.
authors.forename: Jill
authors.initials: J
authors.lastname: Hamilton
authors.affiliation: Department of Psychology, Université du Québec à Montréal, Montreal, QC, Canada.
authors.forename: Ellen
authors.initials: E
authors.lastname: Moss
authors.affiliation: Centre for Child Development and Mental Health, Jewish General Hospital, McGill University, Montreal, QC, Canada.
authors.forename: Ashley
authors.initials: A
authors.lastname: Wazana
authors.affiliation: Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, QC, Canada.|Department of Psychiatry and Neurology, McGill University, Montreal, QC, Canada.
authors.forename: Michael
authors.initials: M
authors.lastname: Meaney
mesh_terms: D002170:Canada; D002675:Child, Preschool; D015331:Cohort Studies; D005260:Female; D059647:Gene-Environment Interaction; D006801:Humans; D008297:Male; D008425:Maternal Behavior / Q000523:psychology*; D009034:Mother-Child Relations / Q000523:psychology*; D009426:Netherlands; D009765:Obesity / Q000235:genetics / Q000523:psychology; D050177:Overweight / Q000235:genetics* / Q000523:psychology*; D050638:Receptors, Dopamine D4 / Q000235:genetics*; D012306:Risk; D012737:Sex Factors
chemical_list: C493599:DRD4 protein, human; D050638:Receptors, Dopamine D4
keywords: DRD4; Maternal sensitivity; obesity; sex differences