Circulating chemerin levels are determined through circulating platelet counts in nondiabetic Taiwanese people: A bidirectional Mendelian randomization study

Lung-An Hsu; Hsin-Hua Chou; Ming-Sheng Teng; Semon Wu; Yu-Lin Ko

doi:10.1016/j.atherosclerosis.2021.01.014

Circulating chemerin levels are determined through circulating platelet counts in nondiabetic Taiwanese people: A bidirectional Mendelian randomization study

Atherosclerosis. 2021 Mar:320:61-69. doi: 10.1016/j.atherosclerosis.2021.01.014. Epub 2021 Jan 19.

Authors

Lung-An Hsu¹, Hsin-Hua Chou², Ming-Sheng Teng³, Semon Wu⁴, Yu-Lin Ko⁵

Affiliations

¹ The First Cardiovascular Division, Department of Internal Medicine, Chang Gung Memorial Hospital, Chang Gung University College of Medicine, Taiwan.
² Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan; School of Medicine, Tzu Chi University, Taiwan.
³ Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan.
⁴ Department of Life Science, Chinese Culture University, Taiwan.
⁵ Cardiovascular Center and Division of Cardiology, Department of Internal Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan; School of Medicine, Tzu Chi University, Taiwan; Department of Research, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, Taiwan. Electronic address: yulinkotco@tzuchi.com.tw.

PMID: 33545615
DOI: 10.1016/j.atherosclerosis.2021.01.014

Abstract

Background and aims: Platelet count (PLT) is a predictor of metabolic and inflammation-related disorders. Platelets can release prochemerin, which acts as a link between coagulation and inflammation and between innate and adaptive immunity. The causal effect between PLT and circulating chemerin level has not been elucidated.

Methods: Nondiabetic participants with samples in the Taiwan Biobank were recruited for a genome-wide association study (GWAS) based on PLT (17,037 participants) and chemerin levels (3887 participants). A bidirectional Mendelian randomization (MR) study was conducted to determine the association between circulating PLT and chemerin levels.

Results: For a GWAS of PLT, 11 gene loci were found to have genome-wide significance. For a GWAS of chemerin levels, two gene loci, RARRES2 and HLADQA2-HLADQB1, were found to have genome-wide significance. Age, sex, body mass index, leukocyte count, hemoglobin, mean blood pressure, hemoglobin A1C, serum total bilirubin, aspartate aminotransferase, triglyceride, and low-density-lipoprotein cholesterol levels, estimated glomerular filtration rate, and circulating chemerin level were found to be independently associated with PLT through a stepwise regression analysis. A bidirectional MR study revealed weighted genetic risk scores (WGRSs) for PLT were significantly associated with chemerin levels by using a two-stage least-square method in a multivariate analysis (p = 0.0031), and no significant association between chemerin level WGRSs and PLT was noted. Sensitivity analysis further revealed no violation of the exclusion-restriction assumption with PLT-determining genotypes on chemerin levels.

Conclusions: Through a bidirectional MR analysis, our data revealed that chemerin levels were determined based on circulating PLT. Circulating chemerin levels can be intermediates between PLT and future metabolic and inflammation-related disorders.

Keywords: Bidirectional Mendelian randomization study; Chemerin level; Genome-wide association study; Platelet count.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Chemokines / genetics
Genome-Wide Association Study*
Intercellular Signaling Peptides and Proteins / genetics
Mendelian Randomization Analysis*
Platelet Count
Taiwan

Substances

Chemokines
Intercellular Signaling Peptides and Proteins