RT Journal
A1 Belsky DW, Moffitt TE, Houts R, et al
T1 Polygenic risk, rapid childhood growth, and the development of obesity: Evidence from a 4-decade longitudinal study
JF Archives of Pediatrics & Adolescent Medicine
JO Archives of Pediatrics & Adolescent Medicine
YR 2012
FD June 1
VO 166
IS 6
SP 515
OP 521
DO 10.1001/archpediatrics.2012.131
UL http://dx.doi.org/10.1001/archpediatrics.2012.131
AB 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.