The Influence of Obesity-Related Single Nucleotide Polymorphisms on BMI Across the Life Course

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  1. Kari E. North1,18
  1. 1Department of Epidemiology, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  2. 2Carolina Population Center, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  3. 3Department of Nutrition, School of Public Health, University of North Carolina at Chapel Hill, Chapel Hill, North Carolina
  4. 4Epidemiology Program, University of Hawaii Cancer Center, Honolulu, Hawaii
  5. 5Vanderbilt Epidemiology Center, Vanderbilt University Medical Center, Nashville, Tennessee
  6. 6Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
  7. 7Center for Human Genetics Research, Vanderbilt University Medical Center, Nashville, Tennessee
  8. 8Division of Epidemiology and Community Health, University of Minnesota School of Public Health, Minneapolis, Minnesota
  9. 9Department of Preventive Medicine, Keck School of Medicine/USC Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California
  10. 10Brigham and Women’s Hospital, Harvard Medical School, Boston, Massachusetts
  11. 11Department of Medicine, University of Pittsburgh, Pittsburgh, Pennsylvania
  12. 12Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, Washington
  13. 13Department of Laboratory Medicine and Pathology, Medical School, University of Minnesota, Minneapolis, Minnesota
  14. 14Department of Statistics and Biostatistics, Rutgers University, Piscataway, New Jersey
  15. 15Department of Genetics, Rutgers University, Piscataway, New Jersey
  16. 16Department of Biostatistics, University of Washington, Seattle, Washington
  17. 17Office of Population Genomics, National Human Genome Research Institute, National Institutes of Health, Bethesda, Maryland
  18. 18Carolina Center for Genome Sciences, School of Public Health, University of North Carolina, Chapel Hill, North Carolina
  1. Corresponding authors: Kari E. North, kari_north{at}unc.edu, and Mariaelisa Graff, migraff{at}email.unc.edu.

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 of Genomics and Epidemiology 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.

  • Received June 27, 2012.
  • Accepted November 26, 2012.

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