Using genetic variants to assess the relationship between circulating lipids and type 2 diabetes.

Research output: Contribution to journalArticle

Abstract

The effects of dyslipidemia on the risk of type 2 diabetes (T2D) and related traits are not clear. We used regression models and 140 lipid-associated genetic variants to estimate associations between circulating HDL-cholesterol, LDL-cholesterol and triglycerides, and T2D and related traits. Each genetic test was corrected for effects of variants on the other two lipid types and surrogates of adiposity. We used the largest datasets available - 34,840 T2D cases and 114,981 controls from the DIAGRAM consortium and up to 133,010 non-diabetic individuals for insulin secretion and sensitivity, from the MAGIC and GENESIS studies.Eight out of 21 associations between groups of variants and diabetes traits were significant at the nominal level, including those between genetically determined lower HDL-C (β=-0.12, P=0.03) and T2D, and genetically determined lower LDL-C (β =-0.21, P=5x10(-6)) and T2D. While some of these may represent causal associations, we discuss why caution must be used when using Mendelian randomization in the context of circulating lipid levels and diabetes traits. In conclusion, we found evidence of links between genetic variants associated with lipids and T2D, but deepened knowledge of the underlying genetic mechanisms of specific lipid variants is needed before drawing definite conclusions about causality using Mendelian randomization methodology.

Details

Authors
  • Tove Fall
  • Weijia Xie
  • Wenny Poon
  • Hanieh Yaghootkar
  • Reedik Mägi
  • Joshua W Knowles
  • Valeriya Lyssenko
  • Michael Weedon
  • Timothy M Frayling
  • Erik Ingelsson
Organisations
Research areas and keywords

Subject classification (UKÄ) – MANDATORY

  • Endocrinology and Diabetes
Original languageEnglish
Pages (from-to)2676-2684
JournalDiabetes
Volume64
Issue number7
Publication statusPublished - 2015
Publication categoryResearch
Peer-reviewedYes