Mendelian Randomization Analysis Support Causal Associations of HbA1c with Circulating Triglyceride, Total and Low-density Lipoprotein Cholesterol in a Chinese Population

Sci Rep. 2019 Apr 2;9(1):5525. doi: 10.1038/s41598-019-41076-6.

Abstract

Previous observational studies supported a positive association of glycated hemoglobin A1c (HbA1c) level with serum triglyceride (TG), total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). However, the causal relationship between HbA1c and either one of them was unclear in the East Asians. We performed a Mendelian Randomization (MR) analysis in a community-based study sample in Shanghai, China (n = 11,935). To clarify the cause-and-effect relationships of HbA1c with the four interested lipids, an Expanded HbA1c genetic risk score (GRS) with 17 HbA1c-related common variants and a Conservative score by excluding 11 variants were built and adopted as the Instrumental Variables (IVs), respectively. The Expanded HbA1c-GRS was associated with 0.19 unit increment in log-TG (P = 0.009), 0.42 mmol/L TC (P = 0.01), and 0.33 mmol/L LDL-C (P = 0.01); while the Conservative HbA1c-GRS was associated with 0.22 unit in log-TG (P = 0.03), 0.60 mmol/L TC (P = 0.01), and 0.51 mmol/L LDL-C (P = 0.007). No causal relationship was detected for HDL-C. Sensitivity analysis supported the above findings. In conclusions, MR analysis supports a causal role of increased HbA1c level in increment of circulating TG, TC, and LDL-C in a Chinese population.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • China
  • Cholesterol, LDL / blood*
  • Female
  • Genetic Variation
  • Glycated Hemoglobin / genetics*
  • Humans
  • Longitudinal Studies
  • Male
  • Mendelian Randomization Analysis / methods*
  • Middle Aged
  • Triglycerides / blood*

Substances

  • Cholesterol, LDL
  • Glycated Hemoglobin A
  • Triglycerides