Polygenic Risk, Appetite Traits, and Weight Gain in Middle Childhood: A Longitudinal Study | Genetics and Genomics | JAMA Pediatrics | JAMA Network
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Skinner  AC, Perrin  EM, Moss  LA, Skelton  JA.  Cardiometabolic risks and severity of obesity in children and young adults .  N Engl J Med. 2015;373(14):1307-1317.PubMedGoogle ScholarCrossref
Singh  AS, Mulder  C, Twisk  JWR, van Mechelen  W, Chinapaw  MJM.  Tracking of childhood overweight into adulthood: a systematic review of the literature .  Obes Rev. 2008;9(5):474-488.PubMedGoogle ScholarCrossref
Yang  W, Kelly  T, He  J.  Genetic epidemiology of obesity .  Epidemiol Rev. 2007;29:49-61.PubMedGoogle ScholarCrossref
Fall  T, Ingelsson  E.  Genome-wide association studies of obesity and metabolic syndrome .  Mol Cell Endocrinol. 2014;382(1):740-757.PubMedGoogle ScholarCrossref
Elks  CE, Heude  B, de Zegher  F,  et al.  Associations between genetic obesity susceptibility and early postnatal fat and lean mass: an individual participant meta-analysis .  JAMA Pediatr. 2014;168(12):1122-1130.PubMedGoogle ScholarCrossref
Belsky  DW, Moffitt  TE, Houts  R,  et al.  Polygenic risk, rapid childhood growth, and the development of obesity: evidence from a 4-decade longitudinal study .  Arch Pediatr Adolesc Med. 2012;166(6):515-521.PubMedGoogle ScholarCrossref
Warrington  NM, Howe  LD, Wu  YY,  et al.  Association of a body mass index genetic risk score with growth throughout childhood and adolescence .  PLoS One. 2013;8(11):e79547.PubMedGoogle ScholarCrossref
Belsky  DW.  Appetite for prevention: genetics and developmental epidemiology join forces in obesity research .  JAMA Pediatr. 2014;168(4):309-311.PubMedGoogle ScholarCrossref
Carnell  S, Wardle  J.  Appetitive traits and child obesity: measurement, origins and implications for intervention .  Proc Nutr Soc. 2008;67(4):343-355.PubMedGoogle ScholarCrossref
Carnell  S, Wardle  J.  Appetite and adiposity in children: evidence for a behavioral susceptibility theory of obesity .  Am J Clin Nutr. 2008;88(1):22-29.PubMedGoogle Scholar
Wardle  J, Carnell  S.  Appetite is a heritable phenotype associated with adiposity .  Ann Behav Med. 2009;38(suppl 1):S25-S30.PubMedGoogle ScholarCrossref
Llewellyn  CH, van Jaarsveld  CHM, Boniface  D, Carnell  S, Wardle  J.  Eating rate is a heritable phenotype related to weight in children .  Am J Clin Nutr. 2008;88(6):1560-1566.PubMedGoogle ScholarCrossref
Llewellyn  CH, van Jaarsveld  CHM, Plomin  R, Fisher  A, Wardle  J.  Inherited behavioral susceptibility to adiposity in infancy: a multivariate genetic analysis of appetite and weight in the Gemini birth cohort .  Am J Clin Nutr. 2012;95(3):633-639.PubMedGoogle ScholarCrossref
Carnell  S, Wardle  J.  Appetitive traits in children. New evidence for associations with weight and a common, obesity-associated genetic variant .  Appetite. 2009;53(2):260-263.PubMedGoogle ScholarCrossref
Wardle  J, Carnell  S, Haworth  CMA, Farooqi  IS, O’Rahilly  S, Plomin  R.  Obesity associated genetic variation in FTO is associated with diminished satiety .  J Clin Endocrinol Metab. 2008;93(9):3640-3643.PubMedGoogle ScholarCrossref
Llewellyn  CH, Trzaskowski  M, van Jaarsveld  CHM, Plomin  R, Wardle  J.  Satiety mechanisms in genetic risk of obesity .  JAMA Pediatr. 2014;168(4):338-344.PubMedGoogle ScholarCrossref
van Jaarsveld  CHM, Llewellyn  CH, Johnson  L, Wardle  J.  Prospective associations between appetitive traits and weight gain in infancy .  Am J Clin Nutr. 2011;94(6):1562-1567.PubMedGoogle ScholarCrossref
Taylor  RW, Grant  AM, Goulding  A, Williams  SM.  Early adiposity rebound: review of papers linking this to subsequent obesity in children and adults .  Curr Opin Clin Nutr Metab Care. 2005;8(6):607-612.PubMedGoogle ScholarCrossref
Norwegian Institute of Public Health. Overweight and obesity in Norway: fact sheet. http://www.fhi.no/eway/default.aspx?pid=240&trg=MainContent_6894&Main_6664=6894:0:25,7585:1:0:0:0:0&MainContent_6894=6706:0:25,7612:1:0:0:0:0. Accessed March 11, 2015.
Crone  MR, Vogels  AGC, Hoekstra  F, Treffers  PDA, Reijneveld  SA.  A comparison of four scoring methods based on the parent-rated Strengths and Difficulties Questionnaire as used in the Dutch preventive child health care system .  BMC Public Health. 2008;8:106.PubMedGoogle ScholarCrossref
Statistics Norway. Population's level of education. http://www.ssb.no/en/utdanning/statistikker/utniv/aar. Accessed June 18, 2013.
Júlíusson  PB, Roelants  M, Nordal  E,  et al.  Growth references for 0–19-year-old Norwegian children for length/height, weight, body mass index and head circumference .  Ann Hum Biol. 2013;40(3):220-227.PubMedGoogle ScholarCrossref
McCarthy  MI.  Genomics, type 2 diabetes, and obesity .  N Engl J Med. 2010;363(24):2339-2350.PubMedGoogle ScholarCrossref
Belsky  DW, Moffitt  TE, Caspi  A.  Genetics in population health science: strategies and opportunities .  Am J Public Health. 2013;103(suppl 1):S73-S83.PubMedGoogle ScholarCrossref
Dudbridge  F.  Power and predictive accuracy of polygenic risk scores .  PLoS Genet. 2013;9(3):e1003348.PubMedGoogle ScholarCrossref
Speliotes  EK, Willer  CJ, Berndt  SI,  et al; MAGIC; Procardis Consortium.  Association analyses of 249,796 individuals reveal 18 new loci associated with body mass index .  Nat Genet. 2010;42(11):937-948.PubMedGoogle ScholarCrossref
Cole  TJ, Freeman  JV, Preece  MA.  Body mass index reference curves for the UK, 1990 .  Arch Dis Child. 1995;73(1):25-29.PubMedGoogle ScholarCrossref
Cole  TJ, Freeman  JV, Preece  MA.  British 1990 growth reference centiles for weight, height, body mass index and head circumference fitted by maximum penalized likelihood .  Stat Med. 1998;17(4):407-429.PubMedGoogle ScholarCrossref
LMSgrowth [computer program]. Version 2.77. Harlow Printing Limited; 2012.
Wardle  J, Guthrie  CA, Sanderson  S, Rapoport  L.  Development of the children’s eating behaviour questionnaire .  J Child Psychol Psychiatry. 2001;42(7):963-970.PubMedGoogle ScholarCrossref
Carnell  S, Wardle  J.  Measuring behavioural susceptibility to obesity: validation of the child eating behaviour questionnaire .  Appetite. 2007;48(1):104-113.PubMedGoogle ScholarCrossref
Mallan  KM, Nambiar  S, Magarey  AM, Daniels  LA.  Satiety responsiveness in toddlerhood predicts energy intake and weight status at four years of age .  Appetite. 2014;74:79-85.PubMedGoogle ScholarCrossref
Ashcroft  J, Semmler  C, Carnell  S, van Jaarsveld  CHM, Wardle  J.  Continuity and stability of eating behaviour traits in children .  Eur J Clin Nutr. 2008;62(8):985-990.PubMedGoogle ScholarCrossref
Webber  L, Hill  C, Saxton  J, Van Jaarsveld  CHM, Wardle  J.  Eating behaviour and weight in children .  Int J Obes (Lond). 2009;33(1):21-28.PubMedGoogle ScholarCrossref
Croker  H, Cooke  L, Wardle  J.  Appetitive behaviours of children attending obesity treatment .  Appetite. 2011;57(2):525-529.PubMedGoogle ScholarCrossref
MacKinnon  D.  Introduction to Statistical Mediation Analysis. Hoboken, NJ: Taylor and Francis; 2012.
Domingue  BW, Belsky  DW, Harris  KM, Smolen  A, McQueen  MB, Boardman  JD.  Polygenic risk predicts obesity in both white and black young adults .  PLoS One. 2014;9(7):e101596.PubMedGoogle ScholarCrossref
Muthèn  LK, Muthèn  BO.  Mplus User’s guide. Sixth Edition. Los Angeles: Muthen & Muthen; 1998-2010.
Elks  CE, Loos  RJF, Hardy  R,  et al.  Adult obesity susceptibility variants are associated with greater childhood weight gain and a faster tempo of growth: the 1946 British Birth Cohort Study .  Am J Clin Nutr. 2012;95(5):1150-1156.PubMedGoogle ScholarCrossref
Steinsbekk  S, Wichstrøm  L.  Predictors of change in BMI from the age of 4 to 8 .  J Pediatr Psychol. 2015;40(10):1056-1064.PubMedGoogle ScholarCrossref
Locke  AE, Kahali  B, Berndt  SI,  et al; LifeLines Cohort Study; ADIPOGen Consortium; AGEN-BMI Working Group; CARDIOGRAMplusC4D Consortium; CKDGen Consortium; GLGC; ICBP; MAGIC Investigators; MuTHER Consortium; MIGen Consortium; PAGE Consortium; ReproGen Consortium; GENIE Consortium; International Endogene Consortium.  Genetic studies of body mass index yield new insights for obesity biology .  Nature. 2015;518(7538):197-206.PubMedGoogle ScholarCrossref
Original Investigation
February 1, 2016

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

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

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.