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

Graff M, Gordon-Larsen P, Lim U, Fowke JH, Love SA, Fesinmeyer M, Wilkens LR, Vertilus S, Ritchie MD, Prentice RL, Pankow J, Monroe K, Manson JE, Le Marchand L, Kuller LH, Kolonel LN, Hong CP, Henderson BE, Haessler J, Gross MD, Goodloe R, Franceschini N, Carlson CS, Buyske S, Bůžková P, Hindorff LA, Matise TC, Crawford DC, Haiman CA, Peters U, North KE
Diabetes. 2013 62 (5): 1763-7

PMID: 23300277 · PMCID: PMC3636619 · DOI:10.2337/db12-0863

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.

MeSH Terms (21)

Adolescent Adult Aged Aged, 80 and over Aging Alpha-Ketoglutarate-Dependent Dioxygenase FTO Body Mass Index Cohort Studies Cross-Sectional Studies European Continental Ancestry Group Female Genetic Association Studies Health Surveys Humans Male Middle Aged Obesity Polymorphism, Single Nucleotide Proteins United States Young Adult

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