TY - JOUR T1 - The influence of obesity-related single nucleotide polymorphisms on BMI across the life course: the PAGE study. JF - Diabetes Y1 - 2013 A1 - Graff, Mariaelisa A1 - Gordon-Larsen, Penny A1 - Lim, Unhee A1 - Fowke, Jay H A1 - Love, Shelly-Ann A1 - Fesinmeyer, Megan A1 - Wilkens, Lynne R A1 - Vertilus, Shawyntee A1 - Ritchie, Marilyn D A1 - Prentice, Ross L A1 - Pankow, Jim A1 - Monroe, Kristine A1 - Manson, JoAnn E A1 - Le Marchand, Loïc A1 - Kuller, Lewis H A1 - Kolonel, Laurence N A1 - Hong, Ching P A1 - Henderson, Brian E A1 - Haessler, Jeff A1 - Gross, Myron D A1 - Goodloe, Robert A1 - Franceschini, Nora A1 - Carlson, Christopher S A1 - Buyske, Steven A1 - Bůzková, Petra A1 - Hindorff, Lucia A A1 - Matise, Tara C A1 - Crawford, Dana C A1 - Haiman, Christopher A A1 - Peters, Ulrike A1 - North, Kari E KW - Adolescent KW - Adult KW - Aged KW - Aged, 80 and over KW - Aging KW - Body Mass Index KW - Cohort Studies KW - Cross-Sectional Studies KW - European Continental Ancestry Group KW - Female KW - Genetic Association Studies KW - Health Surveys KW - Humans KW - Male KW - Middle Aged KW - Obesity KW - Polymorphism, Single Nucleotide KW - Proteins KW - United States KW - Young Adult AB -

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.

VL - 62 IS - 5 U1 - http://www.ncbi.nlm.nih.gov/pubmed/23300277?dopt=Abstract ER -