title: The influence of obesity-related single nucleotide polymorphisms on BMI across the life course: the PAGE study.
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.
authors.affiliation: Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina, USA.
authors.forename: Mariaelisa
authors.initials: M
authors.lastname: Graff
authors.forename: Penny
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authors.lastname: Gordon-Larsen
authors.forename: Unhee
authors.initials: U
authors.lastname: Lim
authors.forename: Jay H
authors.initials: JH
authors.lastname: Fowke
authors.forename: Shelly-Ann
authors.initials: SA
authors.lastname: Love
authors.forename: Megan
authors.initials: M
authors.lastname: Fesinmeyer
authors.forename: Lynne R
authors.initials: LR
authors.lastname: Wilkens
authors.forename: Shawyntee
authors.initials: S
authors.lastname: Vertilus
authors.forename: Marilyn D
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authors.lastname: Ritchie
authors.forename: Ross L
authors.initials: RL
authors.lastname: Prentice
authors.forename: Jim
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authors.lastname: Pankow
authors.forename: Kristine
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authors.lastname: Monroe
authors.forename: JoAnn E
authors.initials: JE
authors.lastname: Manson
authors.forename: Loïc
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authors.lastname: Le Marchand
authors.forename: Lewis H
authors.initials: LH
authors.lastname: Kuller
authors.forename: Laurence N
authors.initials: LN
authors.lastname: Kolonel
authors.forename: Ching P
authors.initials: CP
authors.lastname: Hong
authors.forename: Brian E
authors.initials: BE
authors.lastname: Henderson
authors.forename: Jeff
authors.initials: J
authors.lastname: Haessler
authors.forename: Myron D
authors.initials: MD
authors.lastname: Gross
authors.forename: Robert
authors.initials: R
authors.lastname: Goodloe
authors.forename: Nora
authors.initials: N
authors.lastname: Franceschini
authors.forename: Christopher S
authors.initials: CS
authors.lastname: Carlson
authors.forename: Steven
authors.initials: S
authors.lastname: Buyske
authors.forename: Petra
authors.initials: P
authors.lastname: Bůžková
authors.forename: Lucia A
authors.initials: LA
authors.lastname: Hindorff
authors.forename: Tara C
authors.initials: TC
authors.lastname: Matise
authors.forename: Dana C
authors.initials: DC
authors.lastname: Crawford
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Ulrike
authors.initials: U
authors.lastname: Peters
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D015331:Cohort Studies; D003430:Cross-Sectional Studies; D005260:Female; D056726:Genetic Association Studies; D006306:Health Surveys; D006801:Humans; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics* / Q000378:metabolism; D014481:United States; D044465:White People; D055815:Young Adult
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human