The Influence of Obesity-Related Single Nucleotide Polymorphisms on BMI across the Life Course: The PAGE Study

Download as .RIS

Citation

Graff, Mariaelisa; Gordon-Larsen, Penny; Lim, Unhee; Fowke, Jay H.; Love, Shelly-Ann M.; Fesinmeyer, Megan D.; Wilkens, Lynne R.; Vertilus, Shawyntee; Ritchie, Marylyn D.; & Prentice, Ross L., et al. (2013). The Influence of Obesity-Related Single Nucleotide Polymorphisms on BMI across the Life Course: The PAGE Study. Diabetes, 62(5), 1763-1767. PMCID: PMC3636619

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 of Genomics and Epidemiology 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 (beta [SE] = 1.17 [0.45] vs. 0.09 [0.09] kg/m(2), 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.

URL

http://dx.doi.org/10.2337/db12-0863

Reference Type

Journal Article

Year Published

2013

Journal Title

Diabetes

Author(s)

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

PMCID

PMC3636619

ORCiD

Gordon-Larsen - 0000-0001-5322-4188
Graff - 0000-0001-6380-1735