We're unable to sign you in at this time. Please try again in a few minutes.
We were able to sign you in, but your subscription(s) could not be found. Please try again in a few minutes.
There may be a problem with your account. Please contact the AMA Service Center to resolve this issue.
Contact the AMA Service Center:
Telephone: 1 (800) 262-2350 or 1 (312) 670-7827  *   Email: subscriptions@jamanetwork.com
Error Message ......
Original Investigation |

Polygenic Risk, Appetite Traits, and Weight Gain in Middle Childhood A Longitudinal Study Online Only

Silje Steinsbekk, PhD1; Daniel Belsky, PhD2; Ismail Cuneyt Guzey, MD, PhD3; Jane Wardle, PhD4; Lars Wichstrøm, PhD5
[+] Author Affiliations
1Department of Psychology, Norwegian University of Science and Technology, Trondheim, Norway
2Department of Medicine, Duke University School of Medicine & Social Science Research Institute, Durham, North Carolina
3Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway
4Cancer Research UK Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, London, United Kingdom
5Department of Social Science, Norwegian University of Science and Technology, Trondheim, Norway
JAMA Pediatr. 2016;170(2):e154472. doi:10.1001/jamapediatrics.2015.4472.
Text Size: A A A
Published online

Importance  Genome-wide association studies have identified genetic risks for obesity. These genetic risks influence development of obesity partly by accelerating weight gain in childhood. Research is needed to identify mechanisms to inform intervention. Cross-sectional studies suggest appetite traits as a candidate mechanism. Longitudinal studies are needed to test whether appetite traits mediate genetic influences on children’s weight gain.

Objective  To test whether genetic risk for obesity predicts accelerated weight gain in middle childhood (ages 4-8 years) and whether genetic association with accelerated weight gain is mediated by appetite traits.

Design, Setting, and Participants  Longitudinal study of a representative birth cohort at the Trondheim Early Secure Study, Trondheim, Norway, enrolled at age 4 years during 2007 to 2008, with follow-ups at ages 6 and 8 years. Participants were sampled from all children born in 2003 or 2004 who attended regular community health checkups for 4-year-olds (97.2% attendance; 82.0% consent rate, n = 2475). Nine hundred ninety-five children participated at age 4 years, 795 at age 6 years, and 699 at age 8 years. Analyses included 652 children with genotype, adiposity, and appetite data.

Main Outcomes and Measures  Outcomes were body mass index and body-fat phenotypes measured from anthropometry (ages 4, 6, and 8 years) and bioelectrical impedance (ages 6 and 8 years). Genetic risk for obesity was measured using a genetic risk score composed of 32 single-nucleotide polymorphisms previously discovered in genome-wide association studies of adult body mass index. Appetite traits were measured at age 6 years with the Children’s Eating Behavior Questionnaire.

Results  Of the 652 genotyped child participants, 323 (49.5%) were female, 58 (8.9%) were overweight, and 1 (0.2%) was obese. Children at higher genetic risk for obesity had higher baseline body mass index and fat mass compared with lower genetic risk peers, and they gained weight and fat mass more rapidly during follow-up. Each SD increase in genetic risk score was associated with a 0.22-point increase in BMI at age-4 baseline (for the intercept, unstandardized path coefficient B = 0.22 [95% CI, 0.06-0.38]; P = .008. Children with higher genetic risk scores also gained BMI points more rapidly from ages 4 to 6 years (B = 0.11 [95% CI, 0.03-0.20]; P = .01 ; β = 0.12) and from 6 to 8 years (B = 0.09 [95% CI, 0.00-0.19]; P = .05; β = 0.10), compared with their lower genetic risk peers. Children at higher genetic risk had higher levels of alleged obesogenic appetite traits than peers with lower genetic risk at age 6 years, but appetite traits did not mediate genetic associations with weight gain. The sum of the 5 indirect effects was B = −0.001 (95% CI, −0.02 -0.01); P = .86; β = 0.00.

Conclusions and Relevance  Genetic risk for obesity is associated with accelerated childhood weight gain. Interventions targeting childhood weight gain may provide one path to mitigating genetic risk. However, middle childhood appetite traits may not be a promising target for such interventions. Studies of early-childhood samples are needed to test whether appetite traits explain how genetic risks accelerate growth earlier in development.

Figures in this Article

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?


Place holder to copy figure label and caption
Figure 1.
Sample Recruitment and Follow-up
Graphic Jump Location
Place holder to copy figure label and caption
Figure 2.
Path Model Showing Hypothesized Mediation of Genetic Influence on Children’s Adiposity Gain by Appetite Traits

Figure 2 shows a visual schematic of the path model used to test mediation of genetic associations with adiposity gain by appetite traits. The mediation model included 5 appetite traits: enjoyment of food, emotional overeating, food responsiveness, satiety responsiveness, and slowness in eating. We calculated the portion of the genetic association with growth mediated by appetite traits (the total indirect effect) as the sum of product terms (A path × B path) for each appetite trait. The data table shows coefficient estimates and product terms for each of the A and B paths used to test mediation. To calculate the sums of A and B paths, we reversed path coefficients for satiety responsiveness and slowness in eating because these appetite traits are protective of obesity (ie, higher values indicate lower obesity risk). 95% CI estimates that do not include zero indicate statistically significant estimates at P < .05. Coefficients for additional model paths are reported in eTable 3 in the Supplement. BMI indicates body mass index; GRS indicates Genetic Risk Score.

Graphic Jump Location




Also Meets CME requirements for:
Browse CME for all U.S. States
Accreditation Information
The American Medical Association is accredited by the Accreditation Council for Continuing Medical Education to provide continuing medical education for physicians. The AMA designates this journal-based CME activity for a maximum of 1 AMA PRA Category 1 CreditTM per course. Physicians should claim only the credit commensurate with the extent of their participation in the activity. Physicians who complete the CME course and score at least 80% correct on the quiz are eligible for AMA PRA Category 1 CreditTM.
Note: You must get at least of the answers correct to pass this quiz.
Please click the checkbox indicating that you have read the full article in order to submit your answers.
Your answers have been saved for later.
You have not filled in all the answers to complete this quiz
The following questions were not answered:
Sorry, you have unsuccessfully completed this CME quiz with a score of
The following questions were not answered correctly:
Commitment to Change (optional):
Indicate what change(s) you will implement in your practice, if any, based on this CME course.
Your quiz results:
The filled radio buttons indicate your responses. The preferred responses are highlighted
For CME Course: A Proposed Model for Initial Assessment and Management of Acute Heart Failure Syndromes
Indicate what changes(s) you will implement in your practice, if any, based on this CME course.


Some tools below are only available to our subscribers or users with an online account.

0 Citations

Sign in

Purchase Options

• Buy this article
• Subscribe to the journal
• Rent this article ?

Related Content

Customize your page view by dragging & repositioning the boxes below.

Articles Related By Topic
Related Collections