Satiety Mechanisms in Genetic Risk of Obesity
- 1 April 2014
- journal article
- research article
- Published by American Medical Association (AMA) in JAMA Pediatrics
- Vol. 168 (4), 338-344
- https://doi.org/10.1001/jamapediatrics.2013.4944
Abstract
A better understanding of the cause of obesity is a clinical priority. Obesity is highly heritable, and specific genes are being identified. Discovering the mechanisms through which obesity-related genes influence weight would help pinpoint novel targets for intervention. One potential mechanism is satiety responsiveness. Lack of satiety characterizes many monogenic obesity disorders, and lower satiety responsiveness is linked with weight gain in population samples. To test the hypothesis that satiety responsiveness is an intermediate behavioral phenotype associated with genetic predisposition to obesity in children. Cross-sectional observational study of a population-based cohort of twins born January 1, 1994, to December 31, 1996 (Twins Early Development Study). Participants included 2258 unrelated children (53.3% female; mean [SD] age, 9.9 [0.8] years), one randomly selected from each twin pair. Genetic predisposition to obesity. We created a polygenic risk score (PRS) comprising 28 common obesity-related single-nucleotide polymorphisms identified in a meta-analysis of obesity-related genome-wide association studies. Satiety responsiveness was indexed with a standard psychometric scale (Child Eating Behavior Questionnaire). Using 1990 United Kingdom reference data, body mass index SD scores and waist SD scores were calculated from parent-reported anthropometric data for each child. Information on satiety responsiveness, anthropometrics, and genotype was available for 2258 children. We examined associations among the PRS, adiposity, and satiety responsiveness. The PRS was negatively related to satiety responsiveness (β coefficient, -0.060; 95% CI, -0.019 to -0.101) and positively related to adiposity (β coefficient, 0.177; 95% CI, 0.136-0.218 for body mass index SD scores and β coefficient, 0.167; 95% CI, 0.126-0.208 for waist SD scores). More children in the top 25% of the PRS were overweight than in the lowest 25% (18.5% vs 7.2%; odds ratio, 2.90; 95% CI, 1.98-4.25). Associations between the PRS and adiposity were significantly mediated by satiety responsiveness (P = .006 for body mass index SD scores and P = .005 for waist SD scores). These results support the hypothesis that low satiety responsiveness is one of the mechanisms through which genetic predisposition leads to weight gain in an environment rich with food. Strategies to enhance satiety responsiveness could help prevent weight gain in genetically at-risk children.This publication has 42 references indexed in Scilit:
- First Genome-Wide Association Study on Anxiety-Related Behaviours in ChildhoodPLOS ONE, 2013
- Finding the missing heritability in pediatric obesity: the contribution of genome-wide complex trait analysisInternational Journal of Obesity, 2013
- Polygenic Risk, Rapid Childhood Growth, and the Development of ObesityArchives of Pediatrics & Adolescent Medicine, 2012
- A genome-wide association meta-analysis identifies new childhood obesity lociNature Genetics, 2012
- National, regional, and global trends in body-mass index since 1980: systematic analysis of health examination surveys and epidemiological studies with 960 country-years and 9·1 million participantsThe Lancet, 2011
- Association analyses of 249,796 individuals reveal 18 new loci associated with body mass indexNature Genetics, 2010
- Getting heavier, younger: trajectories of obesity over the life courseInternational Journal of Obesity, 2009
- Genome-wide association study of ulcerative colitis identifies three new susceptibility loci, including the HNF4A regionNature Genetics, 2009
- SNAP: a web-based tool for identification and annotation of proxy SNPs using HapMapBioinformatics, 2008
- A Common Variant in the FTO Gene Is Associated with Body Mass Index and Predisposes to Childhood and Adult ObesityScience, 2007