Complex patterns of direct and indirect association between the transcription Factor-7 like 2 gene, body mass index and type 2 diabetes diagnosis in adulthood in the Hispanic Community Health Study/Study of Latinos

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  • Fernández-Rhodes, Lindsay
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Howard, Annie G
    • Affiliation: Carolina Population Center
  • Graff, Mariaelisa
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Isasi, Carmen R
    • Other Affiliation: Albert Einstein College of Medicine
  • Highland, Heather M
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Young, Kristin L
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
  • Parra, Esteban
    • Other Affiliation: University of Toronto at Mississauga
  • Below, Jennifer E
    • Other Affiliation: Vanderbilt University Medical Center
  • Qi, Qibin
    • Other Affiliation: Albert Einstein College of Medicine
  • Kaplan, Robert C
    • Other Affiliation: Albert Einstein College of Medicine
  • Justice, Anne E
    • Other Affiliation: Geisinger Health System
  • Papanicolaou, George
    • Other Affiliation: National Heart Lung and Blood Institute
  • Laurie, Cathy C
    • Other Affiliation: University of Washington
  • Grant, Struan F A
    • Other Affiliation: Children’s Hospital of Philadelphia Research Institute
  • Haiman, Christopher
    • Other Affiliation: University of Southern California
  • Loos, Ruth J F
    • Other Affiliation: Icahn School of Medicine at Mount Sinai
  • North, Kari E
    • Affiliation: Gillings School of Global Public Health, Department of Epidemiology
Abstract
  • Background Genome-wide association studies have implicated the transcription factor 7-like 2 (TCF7L2) gene in type 2 diabetes risk, and more recently, in decreased body mass index. Given the contrary direction of genetic effects on these two traits, it has been suggested that the observed association with body mass index may reflect either selection bias or a complex underlying biology at TCF7L2. Methods Using 9031 Hispanic/Latino adults (21–76 years) with complete weight history and genetic data from the community-based Hispanic Community Health Study/Study of Latinos (HCHS/SOL, Baseline 2008–2011), we estimated the multivariable association between the additive number of type 2 diabetes increasing-alleles at TCF7L2 (rs7903146-T) and body mass index. We then used structural equation models to simultaneously model the genetic association on changes in body mass index across the life course and estimate the odds of type 2 diabetes per TCF7L2 risk allele. Results We observed both significant increases in type 2 diabetes prevalence at examination (independent of body mass index) and decreases in mean body mass index and waist circumference across genotypes at rs7903146. We observed a significant multivariable association between the additive number of type 2 diabetes-risk alleles and lower body mass index at examination. In our structured modeling, we observed non-significant inverse direct associations between rs7903146-T and body mass index at ages 21 and 45 years, and a significant positive association between rs7903146-T and type 2 diabetes onset in both middle and late adulthood. Conclusions Herein, we replicated the protective effect of rs7930146-T on body mass index at multiple time points in the life course, and observed that these effects were not explained by past type 2 diabetes status in our structured modeling. The robust replication of the negative effects of TCF7L2 on body mass index in multiple samples, including in our diverse Hispanic/Latino community-based sample, supports a growing body of literature on the complex biologic mechanism underlying the functional consequences of TCF7L2 on obesity and type 2 diabetes across the life course.
Date of publication
DOI
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Resource type
  • Article
Rights statement
  • In Copyright
Rights holder
  • The Author(s).
Journal title
  • BMC Obesity
Journal volume
  • 5
Journal issue
  • 1
Page start
  • 26
Language
  • English
Bibliographic citation
  • BMC Obesity. 2018 Oct 02;5(1):26
Publisher
  • BioMed Central

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