Genome-wide association study of serum magnesium in type 2 diabetes.

IF 3.3 3区医学 Q2 GENETICS & HEREDITY

Genes and Nutrition Pub Date : 2024-01-26 DOI:10.1186/s12263-024-00738-5

Lynette J Oost, Roderick C Slieker, Marieke T Blom, Leen M 't Hart, Joost G J Hoenderop, Joline W J Beulens, Jeroen H F de Baaij

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Abstract

People with type 2 diabetes have a tenfold higher prevalence of hypomagnesemia, which is suggested to be caused by low dietary magnesium intake, medication use, and genetics. This study aims to identify the genetic loci that influence serum magnesium concentration in 3466 people with type 2 diabetes. The GWAS models were adjusted for age, sex, eGFR, and HbA1c. Associated traits were identified using publicly available data from GTEx consortium, a human kidney eQTL atlas, and the Open GWAS database. The GWAS identified a genome-wide significant locus in TAF3 (p = 2.9 × 10^-9) in people with type 2 diabetes. In skeletal muscle, loci located in TAF3 demonstrate an eQTL link to ATP5F1C, a gene that is involved in the formation of Mg²⁺-ATP. Serum Mg²⁺ levels were associated with MUC1/TRIM46 (p = 2.9 × 10^-7), SHROOM3 (p = 4.0 × 10^-7), and SLC22A7 (p = 1.0 × 10^-6) at nominal significance, which is in combination with the eQTL data suggesting that they are possible candidates for renal failure. Several genetic loci were in agreement with previous genomic studies which identified MUC1/TRIM46 (P_meta = 6.9 × 10^-29, P_Q = 0.81) and SHROOM3 (P_meta = 2.9 × 10^-27, P_Q = 0.04) to be associated with serum Mg²⁺ in the general population. In conclusion, serum magnesium concentrations are associated with genetic variability around the regions of TAF3, MUC1/TRIM46, SHROOM3, and SLC22A7 in type 2 diabetes.

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2 型糖尿病患者血清镁的全基因组关联研究。

2 型糖尿病患者的低镁血症发病率是普通人的十倍，而低镁血症是由饮食中镁摄入量低、药物使用和遗传因素造成的。本研究旨在确定影响 3466 名 2 型糖尿病患者血清镁浓度的基因位点。GWAS 模型对年龄、性别、eGFR 和 HbA1c 进行了调整。相关性状是利用 GTEx 联合体、人类肾脏 eQTL 图谱和开放 GWAS 数据库中的公开数据确定的。GWAS 在 2 型糖尿病患者的 TAF3（p = 2.9 × 10-9）中发现了一个全基因组显著位点。在骨骼肌中，位于 TAF3 的基因座与 ATP5F1C（一个参与 Mg2+-ATP 形成的基因）有 eQTL 联系。血清 Mg2+ 水平与 MUC1/TRIM46（p = 2.9 × 10-7）、SHROOM3（p = 4.0 × 10-7）和 SLC22A7（p = 1.0 × 10-6）有名义上的显著性关联，这与 eQTL 数据相结合，表明它们可能是肾衰竭的候选基因。几个基因位点与之前的基因组研究一致，之前的研究发现 MUC1/TRIM46（Pmeta = 6.9 × 10-29，PQ = 0.81）和 SHROOM3（Pmeta = 2.9 × 10-27，PQ = 0.04）与普通人群的血清 Mg2+ 相关。总之，2 型糖尿病患者的血清镁浓度与 TAF3、MUC1/TRIM46、SHROOM3 和 SLC22A7 区域的遗传变异有关。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Genes and Nutrition 生物-遗传学

CiteScore

6.60

自引率

0.00%

发文量

审稿时长

6-12 weeks

期刊介绍： This journal examines the relationship between genetics and nutrition, with the ultimate goal of improving human health. It publishes original research articles and review articles on preclinical research data coming largely from animal, cell culture and other experimental models as well as critical evaluations of human experimental data to help deliver products with medically proven use.