Scientific Reports (Apr 2019)

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

  • Xu Jia,
  • Yanan Hou,
  • Min Xu,
  • Zhiyun Zhao,
  • Liping Xuan,
  • Tiange Wang,
  • Mian Li,
  • Yu Xu,
  • Jieli Lu,
  • Yufang Bi,
  • Weiqing Wang,
  • Yuhong Chen

DOI
https://doi.org/10.1038/s41598-019-41076-6
Journal volume & issue
Vol. 9, no. 1
pp. 1 – 9

Abstract

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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.