TY - JOUR
T1 - The influence of obesity-related single nucleotide polymorphisms on BMI across the life course
T2 - The PAGE study
AU - Graff, Mariaelisa
AU - Gordon-Larsen, Penny
AU - Lim, Unhee
AU - Fowke, Jay H.
AU - Love, Shelly Ann
AU - Fesinmeyer, Megan
AU - Wilkens, Lynne R.
AU - Vertilus, Shawyntee
AU - Ritchie, Marilyn D.
AU - Prentice, Ross L.
AU - Pankow, Jim
AU - Monroe, Kristine
AU - Manson, JoAnn E.
AU - Le Marchand, Loïc
AU - Kuller, Lewis H.
AU - Kolonel, Laurence N.
AU - Hong, Ching P.
AU - Henderson, Brian E.
AU - Haessler, Jeff
AU - Gross, Myron D.
AU - Goodloe, Robert
AU - Franceschini, Nora
AU - Carlson, Christopher S.
AU - Buyske, Steven
AU - Bůžková, Petra
AU - Hindorff, Lucia A.
AU - Matise, Tara C.
AU - Crawford, Dana C.
AU - Haiman, Christopher A.
AU - Peters, Ulrike
AU - North, Kari E.
PY - 2013/5
Y1 - 2013/5
N2 - 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.
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.
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U2 - 10.2337/db12-0863
DO - 10.2337/db12-0863
M3 - Article
C2 - 23300277
AN - SCOPUS:84876513251
SN - 0012-1797
VL - 62
SP - 1763
EP - 1767
JO - Diabetes
JF - Diabetes
IS - 5
ER -