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

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Title:	Circulating chemerin levels are determined through circulating platelet counts in nondiabetic Taiwanese people: A bidirectional Mendelian randomization study
Authors:	Hsu, LA (Hsu, Lung-An) Chou, HH (Chou, Hsin-Hua) Teng, MS (Teng, Ming-Sheng) Wu, SM (Wu, Semon) Ko, YL (Ko, Yu -Lin)
Contributors:	生科系
Keywords:	Platelet count Chemerin level Genome-wide association study Bidirectional Mendelian randomization study
Date:	2021-03
Issue Date:	2021-04-14 13:40:17 (UTC+8)
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 as-sociation study (GWAS) based on PLT (17,037 participants) and chemerin levels (3887 participants). A bidi-rectional 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 bili-rubin, 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.
Relation:	ATHEROSCLEROSIS 卷冊: 320 頁數: 61-69
Appears in Collections:	[Department of Biology ] journal articles

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