• Daniel W Belsky, Terrie E Moffitt, Renate Houts, Gary G Bennett, Andrea K Biddle, James A Blumenthal, James P Evans, Honalee Harrington, Karen Sugden, Benjamin Williams, Richie Poulton, and Avshalom Caspi.
• Institute for Genome Sciences and Policy, Duke University, Grey House, Duke University, Durham, NC 27708, USA. dbelsky@duke.edu
• Arch Pediatr Adolesc Med. 2012 Jun 1; 166 (6): 515-21.

ObjectiveTo test how genomic loci identified in genome-wide association studies influence the development of obesity.DesignA 38-year prospective longitudinal study of a representative birth cohort.SettingThe Dunedin Multidisciplinary Health and Development Study, Dunedin, New Zealand.ParticipantsOne thousand thirty-seven male and female study members.Main ExposuresWe assessed genetic risk with a multilocus genetic risk score. The genetic risk score was composed of single-nucleotide polymorphisms identified in genome-wide association studies of obesity-related phenotypes. We assessed family history from parent body mass index data collected when study members were 11 years of age.Main Outcome MeasuresBody mass index growth curves, developmental phenotypes of obesity, and adult obesity outcomes were defined from anthropometric assessments at birth and at 12 subsequent in-person interviews through 38 years of age.ResultsIndividuals with higher genetic risk scores were more likely to be chronically obese in adulthood. Genetic risk first manifested as rapid growth during early childhood. Genetic risk was unrelated to birth weight. After birth, children at higher genetic risk gained weight more rapidly and reached adiposity rebound earlier and at a higher body mass index. In turn, these developmental phenotypes predicted adult obesity, mediating about half the genetic effect on adult obesity risk. Genetic associations with growth and obesity risk were independent of family history, indicating that the genetic risk score could provide novel information to clinicians.ConclusionsGenetic variation linked with obesity risk operates, in part, through accelerating growth in the early childhood years after birth. Etiological research and prevention strategies should target early childhood to address the obesity epidemic.

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