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Inference of a causal relation between low-density lipoprotein cholesterol and hypertension using mendelian

Tae-Hwa Go1,2, Kyeong Im Kwak3, Ji-Yun Jang1,2

  • 1Center of Biomedical Data Science, Yonsei University Wonju College of Medicine, Wonju, Republic of Korea.

Clinical Hypertension
|February 27, 2021
PubMed

Insights

Higher LDL-C levels increase hypertension risk, especially in Koreans. This study used genetic data to confirm a causal link between LDL-C and hypertension, offering new insights into cardiovascular disease prevention.

Area of Science:

  • Cardiovascular Epidemiology
  • Genetic Epidemiology
  • Public Health

Background:

  • Elevated Low-Density Lipoprotein Cholesterol (LDL-C) is linked to cardiovascular disease risk.
  • Causal links between LDL-C and hypertension require further investigation, particularly in Korean populations.
  • Existing studies are limited by observational designs and lack of genetic epidemiology data.

Purpose of the Study:

  • To investigate the causal relationship between LDL-C and hypertension in a Korean cohort.
  • To leverage genetic data for a robust assessment of LDL-C's impact on hypertension risk.
  • To address the lack of genetic epidemiology studies on LDL-C and hypertension in Koreans.

Main Methods:

  • Utilized data from the Korean Genome and Epidemiology Study (20,701 subjects).
  • Selected single-nucleotide polymorphisms (SNPs) associated with LDL-C from the Global Lipids Genetics Consortium.
  • Performed Mendelian randomization analysis (MRA) using genetic risk scores (GRS) for 24 SNPs.

Main Results:

  • Mendelian randomization assumptions were statistically validated.
  • Weighted genetic risk scores (WGRSs) demonstrated a strong association with LDL-C.
  • MRA revealed a statistically significant increase in hypertension risk with rising LDL-C in both sexes, unlike observational findings.

Conclusions:

  • Genetic information significantly influences the relationship between LDL-C and hypertension.
  • Confirms a causal effect of LDL-C on hypertension risk in the Korean population.
  • Highlights the importance of genetic factors in understanding hypertension etiology.
Abstract

Keywords:
Genetic epidemiologyHypertensionLow-density lipoprotein cholesterolMendelian randomization

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