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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.

TitleComplex 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.
Publication TypePublication
Year2018
AuthorsFernández-Rhodes L, Howard AGreen, Graff M, Isasi CR, Highland HM, Young KL, Parra E, Below JE, Qi Q, Kaplan RC, Justice AE, Papanicolaou G, Laurie CC, Grant SFA, Haiman C, Loos RJF, North KE
JournalBMC Obes
Volume5
Pagination26
Date Published2018
ISSN2052-9538
Abstract

Background: Genome-wide association studies have implicated the () 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 .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 (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 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 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 on obesity and type 2 diabetes across the life course.

DOI10.1186/s40608-018-0200-x
Alternate JournalBMC Obes
PubMed ID30305909
PubMed Central IDPMC6167893
Grant ListU01 HG007417 / HG / NHGRI NIH HHS / United States
U01 HG007419 / HG / NHGRI NIH HHS / United States
R01 DK107786 / DK / NIDDK NIH HHS / United States
R01 DK101855 / DK / NIDDK NIH HHS / United States
R56 HG010297 / HG / NHGRI NIH HHS / United States
R01 HD057194 / HD / NICHD NIH HHS / United States
T32 HL007055 / HL / NHLBI NIH HHS / United States
MS#: 
0638
Manuscript Lead/Corresponding Author Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
ECI: 
Manuscript Affiliation: 
Field Center: Bronx (Einstein College of Medicine)
Manuscript Status: 
Published