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Original Investigation |

Genetic Differential Susceptibility to Socioeconomic Status and Childhood Obesogenic Behavior Why Targeted Prevention May Be the Best Societal Investment

Patricia P. Silveira, MD, PhD1; Hélène Gaudreau, PhD2; Leslie Atkinson, PhD3; Alison S. Fleming, PhD4; Marla B. Sokolowski, PhD5; Meir Steiner, MD, PhD6; James L. Kennedy, MD, MSc7; Michael J. Meaney, PhD, CQ, FRSC2; Robert D. Levitan, MD, FRCPC7; Laurette Dubé, BSc, MBA, MPS, PhD8
[+] Author Affiliations
1Department of Pediatrics, Universidade Federal do Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil
2Ludmer Centre for Neuroinformatics and Mental Health, Douglas Mental Health University Institute, McGill University, Montreal, Quèbec, Canada
3Department of Psychology, Ryerson University, Toronto, Ontario, Canada
4Department of Psychology, University of Toronto, Toronto, Ontario, Canada
5Department of Ecology and Evolutionary Biology, University of Toronto, Toronto, Ontario, Canada
6Department of Psychiatry and Behavioural Neurosciences, McMaster University, Hamilton, Ontario, Canada
7Department of Psychiatry, University of Toronto and Centre for Addiction and Mental Health, Toronto, Ontario, Canada
8Desautels Faculty of Management, McGill Center for the Convergence of Health and Economics, McGill University, Montreal, Quebec, Canada
JAMA Pediatr. 2016;170(4):359-364. doi:10.1001/jamapediatrics.2015.4253.
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Importance  Genes may work by modulating the way individuals respond to environmental variation, and these discrete and differential genes vs environmental interactions may not be readily captured in simple association studies.

Objective  To determine whether children carrying the 7-repeat allele of the DRD4 gene living under adverse economic conditions have worse-than-average fat intake compared with those living in a healthy environment.

Design, Setting, and Participants  Data from an established prospective birth cohort (Maternal Adversity, Vulnerability, and Neurodevelopment) were used to study 4-year-old children from Montreal, Quebec, Canada and Hamilton, Ontario, Canada. A total of 190 children (94 girls and 96 boys) had height and weight measured and complete food diaries and were therefore eligible for the study. The study is derived from a birth cohort started in June 2003 and still ongoing. The last age of follow-up was at 6 years.

Exposures  Social environment was characterized based on the gross family income, and DNA was genotyped for the 7-repeat allele of the DRD4 gene.

Main Outcomes and Measures  Fat intake.

Results  The 5 steps to distinguish the differential susceptibility from other types of interaction were followed, and the study confirms that differential susceptibility is a relevant model to address the association between the 7-repeat allele of DRD4 and food choices in girls. Of the 190 children, 112 did not have the DRD4 7-repeat allele and 78 did. Baseline characteristics did not differ in these 2 groups. Although not different in several confounders, such as maternal educational level, maternal smoking during gestation, birth weight, and breastfeeding duration, girls carrying the 7-repeat allele of the DRD4 gene and living in adverse socioeconomic conditions have increased fat intake compared with girls who are noncarriers (DRD4 7+ mean, 33.95% of calories derived from fat; 95% CI, 28.76%-39.13%; DRD4 7− mean, 28.76%; 95% CI, 26.77%-30.83%). However, girls carrying the 7-repeat allele of the same gene and living in better socioeconomic conditions have decreased fat intake compared with noncarriers (DRD4 7+ mean, 29.03% of calories derived from fat; 95% CI, 26.69%-31.51%; DRD4 7− mean, 31.88%; 95% CI, 30.28%-33.58%).

Conclusions and Relevance  Alleles previously considered to be obesity risk alleles might in fact function as plasticity alleles, determining openness to environmental modification and/or intervention, as seen in the girls in this study. This finding has important implications for obesity prevention and social pediatrics.

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Figure 1.
Mean Percentage of Intake of Calories Derived From Fat Among Girls at 4 Years of Age Stratified by DRD4 (7− or 7+) and Income (Below or Above Low-Income Cutoff)19

A 2-way analysis of variance revealed an interaction between the DRD4 genotype and the income categories (P = .005) on the percentage of intake of calories derived from fat, providing evidence for the differential susceptibility model. FFQ indicates food frequency questionnaire; LICO, low-income cutoff; 7−, 7-repeat allele absent; 7+, 7-repeat allele present. Error bars indicate 95% CIs.

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Figure 2.
Comparison of the Regression Plot With the Prototypical Graphic Representing Differential Susceptibility

Differential susceptibility is defined by Belsky et al.11 LICO indicates low-income cutoff; 7−, 7-repeat allele absent; 7+, 7-repeat allele present.

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