Polygenic risk, rapid childhood growth, and the development of obesity: evidence from a 4-decade longitudinal study

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, Avshalom Caspi

Research output: Contribution to journalArticlepeer-review

112 Citations (Scopus)

Abstract

Objective To test how genomic loci identified in genome-wide association studies influence the development of obesity.

Design A 38-year prospective longitudinal study of a representative birth cohort.

Setting The Dunedin Multidisciplinary Health and Development Study, Dunedin, New Zealand.

Participants One thousand thirty-seven male and female study members.

Main Exposures We 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 Measures Body 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.

Results Individuals 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.

Conclusions Genetic 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.
Original languageEnglish
Pages (from-to)515-521
Number of pages7
JournalArchives of pediatrics & adolescent medicine
Volume166
Issue number6
DOIs
Publication statusPublished - Jun 2012

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