The Interaction of Genetic Predisposition and Socioeconomic Position With Type 2 Diabetes Mellitus: Cross-Sectional and Longitudinal Analyses From the Lifelines Cohort and Biobank Study

Psychosom Med. 2018 Apr;80(3):252-262. doi: 10.1097/PSY.0000000000000562.

Abstract

Objective: A strong genetic predisposition for type 2 diabetes mellitus (T2DM) may aggravate the negative effects of low socioeconomic position (SEP) in the etiology of the disorder. This study aimed to examine cross-sectional and longitudinal associations and interactions of a genetic risk score (GRS) and SEP with T2DM and to investigate whether clinical and behavioral risk factors can explain these associations and interactions.

Methods: We used data from 13,027 genotyped participants from the Lifelines study. The GRS was based on single-nucleotide polymorphisms genome-wide associated with T2DM and was categorized into tertiles. SEP was measured as educational level. T2DM was based on biological markers, recorded medication use, and self-reports. Cross-sectional and longitudinal associations and interactions between the GRS and SEP on T2DM were examined.

Results: The combination of a high GRS and low SEP had the strongest association with T2DM in cross-sectional (odds ratio = 3.84, 95% confidence interval = 2.28-6.46) and longitudinal analyses (hazard ratio = 2.71, 1.39-5.27), compared with a low GRS and high SEP. Interaction between a high GRS and a low SEP was observed in cross-sectional (relative excess risk due to interaction = 1.85, 0.65-3.05) but not in longitudinal analyses. Clinical and behavioral risk factors mostly explained the observed associations and interactions.

Conclusions: A high GRS combined with a low SEP provides the highest risk for T2DM. These factors also exacerbated each other's impact cross-sectionally but not longitudinally. Preventive measures should target individual and contextual factors of this high-risk group to reduce the risk of T2DM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Biological Specimen Banks
  • Cross-Sectional Studies
  • Diabetes Mellitus, Type 2* / epidemiology
  • Diabetes Mellitus, Type 2* / etiology
  • Diabetes Mellitus, Type 2* / genetics
  • Female
  • Genetic Predisposition to Disease
  • Genome-Wide Association Study
  • Humans
  • Longitudinal Studies
  • Male
  • Middle Aged
  • Netherlands / epidemiology
  • Polymorphism, Single Nucleotide
  • Social Class*