The influence of obesity-related single nucleotide polymorphisms on BMI across the life course: The PAGE study

Mariaelisa Graff, Penny Gordon-Larsen, Unhee Lim, Jay H. Fowke, Shelly Ann Love, Megan Fesinmeyer, Lynne R. Wilkens, Shawyntee Vertilus, Marilyn D. Ritchie, Ross L. Prentice, Jim Pankow, Kristine Monroe, JoAnn E. Manson, Loïc Le Marchand, Lewis H. Kuller, Laurence N. Kolonel, Ching P. Hong, Brian E. Henderson, Jeff Haessler, Myron D. GrossRobert Goodloe, Nora Franceschini, Christopher S. Carlson, Steven Buyske, Petra Bůžková, Lucia A. Hindorff, Tara C. Matise, Dana C. Crawford, Christopher A. Haiman, Ulrike Peters, Kari E. North

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21 Scopus citations

Abstract

Evidence is limited as to whether heritable risk of obesity varies throughout adulthood. Among >34,000 European Americans, aged 18-100 years, from multiple U.S. studies in the Population Architecture using Genomics and Epidemiology (PAGE) Consortium, we examined evidence for heterogeneity in the associations of five established obesity risk variants (near FTO, GNPDA2, MTCH2, TMEM18, and NEGR1) with BMI across four distinct epochs of adulthood: 1) young adulthood (ages 18-25 years), adulthood (ages 26-49 years), middle-age adulthood (ages 50-69 years), and older adulthood (ages ≥70 years); or 2) by menopausal status in women and stratification by age 50 years in men. Summary-effect estimates from each meta-analysis were compared for heterogeneity across the life epochs. We found heterogeneity in the association of the FTO (rs8050136) variant with BMI across the four adulthood epochs (P = 0.0006), with larger effects in young adults relative to older adults (β [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m2, respectively, per A allele) and smaller intermediate effects. We found no evidence for heterogeneity in the association of GNPDA2, MTCH2, TMEM18, and NEGR1 with BMI across adulthood. Genetic predisposition to obesity may have greater effects on body weight in young compared with older adulthood for FTO, suggesting changes by age, generation, or secular trends. Future research should compare and contrast our findings with results using longitudinal data.

Original languageEnglish (US)
Pages (from-to)1763-1767
Number of pages5
JournalDiabetes
Volume62
Issue number5
DOIs
StatePublished - May 1 2013

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ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism

Cite this

Graff, M., Gordon-Larsen, P., Lim, U., Fowke, J. H., Love, S. A., Fesinmeyer, M., Wilkens, L. R., Vertilus, S., Ritchie, M. D., Prentice, R. L., Pankow, J., Monroe, K., Manson, J. E., Le Marchand, L., Kuller, L. H., Kolonel, L. N., Hong, C. P., Henderson, B. E., Haessler, J., ... North, K. E. (2013). The influence of obesity-related single nucleotide polymorphisms on BMI across the life course: The PAGE study. Diabetes, 62(5), 1763-1767. https://doi.org/10.2337/db12-0863