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

Overview

Journal BMC Obes

Publisher Biomed Central

Date 2018 Oct 12

PMID 30305909

Citations 5

Authors

Lindsay Fernandez-Rhodes

Annie Green Howard

Mariaelisa Graff

Carmen R Isasi

Heather M Highland

Kristin L Young

Esteban Parra

Jennifer E Below

Qibin Qi

Robert C Kaplan

Anne E Justice

George Papanicolaou

Cathy C Laurie

Struan F A Grant

Christopher Haiman

Ruth J F Loos

Kari E North

Affiliations

Soon will be listed here.

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.

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