血浆维生素C与2型糖尿病：欧洲人群的全基因组关联研究和孟德尔随机化分析

Plasma Vitamin C and Type 2 Diabetes: Genome-Wide Association Study and Mendelian Randomization Analysis in European Populations.

作者信息

Zheng Ju-Sheng, Luan Jian'an, Sofianopoulou Eleni, Imamura Fumiaki, Stewart Isobel D, Day Felix R, Pietzner Maik, Wheeler Eleanor, Lotta Luca A, Gundersen Thomas E, Amiano Pilar, Ardanaz Eva, Chirlaque María-Dolores, Fagherazzi Guy, Franks Paul W, Kaaks Rudolf, Laouali Nasser, Mancini Francesca Romana, Nilsson Peter M, Onland-Moret N Charlotte, Olsen Anja, Overvad Kim, Panico Salvatore, Palli Domenico, Ricceri Fulvio, Rolandsson Olov, Spijkerman Annemieke M W, Sánchez María-José, Schulze Matthias B, Sala Núria, Sieri Sabina, Tjønneland Anne, Tumino Rosario, van der Schouw Yvonne T, Weiderpass Elisabete, Riboli Elio, Danesh John, Butterworth Adam S, Sharp Stephen J, Langenberg Claudia, Forouhi Nita G, Wareham Nicholas J

机构信息

Medical Research Council Epidemiology Unit, University of Cambridge, Cambridge, U.K.

Key Laboratory of Growth Regulation and Translational Research of Zhejiang Province, School of Life Sciences, Westlake University, Hangzhou, China.

出版信息

Diabetes Care. 2021 Jan;44(1):98-106. doi: 10.2337/dc20-1328. Epub 2020 Nov 17.

DOI:10.2337/dc20-1328

PMID:33203707

原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7783939/

Abstract

OBJECTIVE

Higher plasma vitamin C levels are associated with lower type 2 diabetes risk, but whether this association is causal is uncertain. To investigate this, we studied the association of genetically predicted plasma vitamin C with type 2 diabetes.

RESEARCH DESIGN AND METHODS

We conducted genome-wide association studies of plasma vitamin C among 52,018 individuals of European ancestry to discover novel genetic variants. We performed Mendelian randomization analyses to estimate the association of genetically predicted differences in plasma vitamin C with type 2 diabetes in up to 80,983 case participants and 842,909 noncase participants. We compared this estimate with the observational association between plasma vitamin C and incident type 2 diabetes, including 8,133 case participants and 11,073 noncase participants.

RESULTS

We identified 11 genomic regions associated with plasma vitamin C ( < 5 × 10), with the strongest signal at , and 10 novel genetic loci including , , , , , , , , , and . Plasma vitamin C was inversely associated with type 2 diabetes (hazard ratio per SD 0.88; 95% CI 0.82, 0.94), but there was no association between genetically predicted plasma vitamin C (excluding variant due to its apparent pleiotropic effect) and type 2 diabetes (1.03; 95% CI 0.96, 1.10).

CONCLUSIONS

These findings indicate discordance between biochemically measured and genetically predicted plasma vitamin C levels in the association with type 2 diabetes among European populations. The null Mendelian randomization findings provide no strong evidence to suggest the use of vitamin C supplementation for type 2 diabetes prevention.

摘要

目的

较高的血浆维生素C水平与较低的2型糖尿病风险相关，但这种关联是否为因果关系尚不确定。为了对此进行研究，我们探讨了基因预测的血浆维生素C与2型糖尿病之间的关联。

研究设计与方法

我们对52018名欧洲血统个体的血浆维生素C进行了全基因组关联研究，以发现新的基因变异。我们进行了孟德尔随机化分析，以估计在多达80983例病例参与者和842909例非病例参与者中，基因预测的血浆维生素C差异与2型糖尿病之间的关联。我们将这一估计值与血浆维生素C与2型糖尿病发病之间的观察性关联进行了比较，后者包括8133例病例参与者和11073例非病例参与者。

结果

我们确定了11个与血浆维生素C相关的基因组区域（<5×10），其中最强的信号位于，以及10个新的基因位点，包括、、、、、、、、、和。血浆维生素C与2型糖尿病呈负相关（每标准差风险比为0.88；95%置信区间为0.82，0.94），但基因预测的血浆维生素C（由于其明显的多效性效应排除变异）与2型糖尿病之间无关联（1.03；95%置信区间为0.96，1.10）。