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Association and Interaction of Genetics and Area-level Socioeconomic Factors on the Prevalence of Type 2 Diabetes and Obesity

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posted on 2023-02-15, 01:08 authored by Sara J. Cromer, Chirag M. Lakhani, Josep Mercader, Timothy D. Majarian, Philipp Schroeder, Joanne B. Cole, Jose C. Florez, Chirag J. Patel, Alisa Manning, Sherri-Ann M. Burnett-Bowie, Jordi Merino, Miriam S. Udler

  

Objective: Quantify the impact of genetic and socioeconomic factors on risk of type 2 diabetes (T2D) and obesity.

Research Design and Methods: Among participants in the Mass General Brigham Biobank (MGBB) and UK Biobank (UKB), we used logistic regression models to calculate cross-sectional odds of T2D and obesity using 1) polygenic risk scores for T2D and body mass index (BMI) and 2) area-level socioeconomic risk (educational attainment) measures. The primary analysis included 26,737 participants of European genetic ancestry in MGBB with replication in UKB (N=223,843), as well as in participants of non-European ancestry (MGBB N=3,468; UKB N=7,459).

Results:  The area-level socioeconomic measure most strongly associated with both T2D and obesity was percent without a college degree, and associations with disease prevalence were independent of genetic risk (P<0.001 for each). Moving from lowest to highest quintiles of combined genetic and socioeconomic burden more than tripled T2D (3.1% to 22.2%) and obesity (20.9% to 69.0%) prevalence. Favorable socioeconomic risk was associated with lower disease prevalence, even in those with highest genetic risk (T2D 13.0% vs. 22.2%, obesity 53.6% vs. 69.0% in lowest vs. highest socioeconomic risk quintiles). Additive effects of genetic and socioeconomic factors accounted for 13.2% and 16.7% of T2D and obesity prevalence explained by these models, respectively. Findings were replicated in independent European and non-European ancestral populations. 

Conclusions: Genetic and socioeconomic factors significantly interact to increase risk of T2D and obesity. Favorable area-level socioeconomic status was associated with an almost 50% lower T2D prevalence in those with high genetic risk.

Funding

American Diabetes Association 7-21-JDFM-005

MGH Department of Medicine

U.S. Department of Health and Human Services > National Institutes of Health F32DK127545 K23DK114551 K24 HL157960 K99DK127196 P30DK040561 R01 HL145025 T32DK007028 U01 HG011723

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