title: Polygenic Risk, Appetite Traits, and Weight Gain in Middle Childhood: A Longitudinal Study.
abstract: OBJECTIVE
  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.
  
  
  METHODS
  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.
  
  
  METHODS
  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
  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.
authors.affiliation: Department of Psychology, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Silje
authors.initials: S
authors.lastname: Steinsbekk
authors.affiliation: Department of Medicine, Duke University School of Medicine & Social Science Research Institute, Durham, North Carolina.
authors.forename: Daniel
authors.initials: D
authors.lastname: Belsky
authors.affiliation: Department of Neuroscience, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Ismail Cuneyt
authors.initials: IC
authors.lastname: Guzey
authors.affiliation: Cancer Research UK Health Behaviour Research Centre, Department of Epidemiology and Public Health, University College London, London, United Kingdom.
authors.forename: Jane
authors.initials: J
authors.lastname: Wardle
authors.affiliation: Department of Social Science, Norwegian University of Science and Technology, Trondheim, Norway.
authors.forename: Lars
authors.initials: L
authors.lastname: Wichstrøm
mesh_terms: D001066:Appetite / Q000235:genetics*; D015992:Body Mass Index; D001835:Body Weight; D002648:Child; D002675:Child, Preschool; D005260:Female; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006801:Humans; D008137:Longitudinal Studies; D008297:Male; D009664:Norway; D063766:Pediatric Obesity / Q000235:genetics*; D012307:Risk Factors; D015430:Weight Gain / Q000235:genetics*
references.citation: Appetite. 2007 Jan;48(1):104-13
references.pmid: 16962207
references.citation: Appetite. 2009 Oct;53(2):260-3
references.pmid: 19635515
references.citation: Ann Behav Med. 2009 Dec;38 Suppl 1:S25-30
references.pmid: 19730964
references.citation: PLoS One. 2014 Jul 03;9(7):e101596
references.pmid: 24992585
references.citation: Ann Hum Biol. 2013 May;40(3):220-7
references.pmid: 23414181
references.citation: J Child Psychol Psychiatry. 2001 Oct;42(7):963-70
references.pmid: 11693591
references.citation: Appetite. 2014 Mar;74:79-85
references.pmid: 24316574
references.citation: Obes Rev. 2008 Sep;9(5):474-88
references.pmid: 18331423
references.citation: PLoS One. 2013 Nov 11;8(11):e79547
references.pmid: 24244521
references.citation: PLoS Genet. 2013 Mar;9(3):e1003348
references.pmid: 23555274
references.citation: Arch Pediatr Adolesc Med. 2012 Jun 1;166(6):515-21
references.pmid: 22665028
references.citation: Am J Clin Nutr. 2012 Mar;95(3):633-9
references.pmid: 22277555
references.citation: Appetite. 2011 Oct;57(2):525-9
references.pmid: 21658420
references.citation: Int J Obes (Lond). 2009 Jan;33(1):21-8
references.pmid: 19002146
references.citation: JAMA Pediatr. 2014 Apr;168(4):338-344
references.pmid: 24535189
references.citation: Eur J Clin Nutr. 2008 Aug;62(8):985-90
references.pmid: 17684526
references.citation: Arch Dis Child. 1995 Jul;73(1):25-9
references.pmid: 7639544
references.citation: Stat Med. 1998 Feb 28;17 (4):407-29
references.pmid: 9496720
references.citation: Epidemiol Rev. 2007;29:49-61
references.pmid: 17566051
references.citation: Nat Genet. 2010 Nov;42(11):937-48
references.pmid: 20935630
references.citation: N Engl J Med. 2015 Oct;373(14):1307-17
references.pmid: 26422721
references.citation: BMC Public Health. 2008 Apr 04;8:106
references.pmid: 18394152
references.citation: J Clin Endocrinol Metab. 2008 Sep;93(9):3640-3
references.pmid: 18583465
references.citation: Am J Clin Nutr. 2008 Jul;88(1):22-9
references.pmid: 18614720
references.citation: Mol Cell Endocrinol. 2014 Jan 25;382(1):740-757
references.pmid: 22963884
references.citation: Curr Opin Clin Nutr Metab Care. 2005 Nov;8(6):607-12
references.pmid: 16205460
references.citation: Am J Clin Nutr. 2011 Dec;94(6):1562-7
references.pmid: 22071702
references.citation: Proc Nutr Soc. 2008 Nov;67(4):343-55
references.pmid: 18715519
references.citation: Am J Clin Nutr. 2008 Dec;88(6):1560-6
references.pmid: 19064516
references.citation: N Engl J Med. 2010 Dec 9;363(24):2339-50
references.pmid: 21142536
references.citation: Nature. 2015 Feb 12;518(7538):197-206
references.pmid: 25673413
references.citation: JAMA Pediatr. 2014 Apr;168(4):309-11
references.pmid: 24535111
references.citation: Am J Clin Nutr. 2012 May;95(5):1150-6
references.pmid: 22456663
references.citation: J Pediatr Psychol. 2015 Nov-Dec;40(10):1056-64
references.pmid: 26050242
references.citation: Am J Public Health. 2013 Oct;103 Suppl 1:S73-83
references.pmid: 23927511
references.citation: JAMA Pediatr. 2014 Dec;168(12):1122-30
references.pmid: 25329327