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, J. H., Love, S., Fesinmeyer, M., Wilkens, L. R., Vertilus, S., Ritchie, M. D., Prentice, R. L., Pankow, J., Monroe, K., Manson, J. E., Le Marchand, L., Kuller, L. H., Kolonel, L. N., Hong, C. P., Henderson, B. E., Haessler, J., Gross, M. D., Goodloe, R., Franceschini, N., Carlson, C. S., Buyske, S., B ̊u ̌zková, P., Hindorff, L. A., Matise, T. C., Crawford, D. C., Haiman, C. A., Peters, U., & North, K. E. Diabetes, 62:1763–1767, May, 2013. ![The influence of obesity-related single nucleotide polymorphisms on BMI across the life course: the PAGE study. [link]](https://bibbase.org/img/filetypes/link.svg "link")
Paper doi abstract bibtex 1 download 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.
@article{GraffGordonLarsenLimEtAl2013,
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.},
author = {Graff, Mariaelisa and Gordon-Larsen, Penny and Lim, Unhee and Fowke, Jay H. and Love, Shelly-Ann and Fesinmeyer, Megan and Wilkens, Lynne R. and Vertilus, Shawyntee and Ritchie, Marilyn D. and Prentice, Ross L. and Pankow, Jim and Monroe, Kristine and Manson, JoAnn E. and Le Marchand, Lo{\"\i}c and Kuller, Lewis H. and Kolonel, Laurence N. and Hong, Ching P. and Henderson, Brian E. and Haessler, Jeff and Gross, Myron D. and Goodloe, Robert and Franceschini, Nora and Carlson, Christopher S. and Buyske, Steven and B{\r u}{\v z}kov{\'a}, Petra and Hindorff, Lucia A. and Matise, Tara C. and Crawford, Dana C. and Haiman, Christopher A. and Peters, Ulrike and North, Kari E.},
chemicals = {Proteins, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, FTO protein, human},
citation-subset = {AIM, IM},
completed = {2013-06-28},
country = {United States},
doi = {10.2337/db12-0863},
issn = {1939-327X},
issn-linking = {0012-1797},
issue = {5},
journal = {Diabetes},
keywords = {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, genetics, metabolism; Polymorphism, Single Nucleotide; Proteins, genetics, metabolism; United States; Young Adult},
month = may,
nlm-id = {0372763},
owner = {NLM},
pages = {1763--1767},
pii = {db12-0863},
pmc = {PMC3636619},
pmid = {23300277},
url = {https://pubmed.ncbi.nlm.nih.gov/23300277/},
pubmodel = {Print-Electronic},
pubstate = {ppublish},
revised = {2018-11-13},
title = {The influence of obesity-related single nucleotide polymorphisms on {BMI} across the life course: the {PAGE} study.},
volume = {62},
year = {2013},
bdsk-url-1 = {https://pubmed.ncbi.nlm.nih.gov/23300277/},
bdsk-url-2 = {https://doi.org/10.2337/db12-0863}}
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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. 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