Centre de recherche de l'Institut universitaire de cardiologie et de pneumologie de Québec, Québec, Canada.
Department of Medicine, Faculty of Medicine, Université Laval, Québec, Canada.
J Clin Endocrinol Metab. 2021 Jul 13;106(8):e3178-e3184. doi: 10.1210/clinem/dgab144.
The impact of galectin-3 inhibitors on nonalcoholic fatty liver diseases (NAFLD)-related outcomes is currently under investigation in randomized clinical trials. Whether there is a causal association between plasma galectin-3 levels and NAFLD is unknown.
To evaluate the causal effect of circulating galectin-3 levels on NAFLD as well as >800 other human diseases.
Inverse variance-weighted (IVW) Mendelian randomization (MR) and phenome-wide MR.
Summary statistics of genome-wide association studies.
Participants of the UK Biobank, Electronic Medical Records and Genomics (eMERGE), FinnGen, Prevention of Renal and Vascular End-Stage Disease (PREVEND), and IMPROVE cohorts.
Identification of independent single-nucleotide polymorphisms (SNPs) associated with galectin-3 levels (P < 5 × 10-8) in the PREVEND (14 SNPs) and IMPROVE (3 SNPs) cohorts.
Presence of NAFLD in a meta-analysis of genome-wide association study of the eMERGE, UK Biobank, and FinnGen cohorts (3042 NAFLD cases and 504 853 controls), as well as >800 other human diseases in the UK Biobank and FinnGen.
Using IVW-MR, we found no causal association between galectin-3 levels and NAFLD in the meta-analysis of the 3 cohorts or in each individual cohort. After correction for multiple testing, we found no causal association between galectin-3 levels and >800 human disease-related traits.
This MR study revealed no causal associations between circulating galectin-3 levels and NAFLD or any other disease traits, suggesting that plasma galectin-3 levels may not be directly implicated in the pathogenesis of NAFLD or other human diseases.
Galectin-3 抑制剂对非酒精性脂肪性肝病（NAFLD）相关结局的影响目前正在随机临床试验中进行研究。血浆 Galectin-3 水平与 NAFLD 之间是否存在因果关系尚不清楚。
评估循环 Galectin-3 水平对 NAFLD 以及 800 多种其他人类疾病的因果效应。
逆方差加权（IVW）孟德尔随机化（MR）和表型全基因组关联研究（PheWAS）MR。
全基因组关联研究的汇总统计数据。
英国生物库、电子病历和基因组学（eMERGE）、芬兰基因组研究（FinnGen）、预防肾脏和血管终末期疾病（PREVEND）和 IMPROVE 队列的参与者。
在 PREVEND（14 个 SNP）和 IMPROVE（3 个 SNP）队列中鉴定与 Galectin-3 水平相关的独立单核苷酸多态性（SNP）（P<5×10-8）。
eMERGE、英国生物库和芬兰基因组研究的全基因组关联研究荟萃分析中 NAFLD 的存在（3042 例 NAFLD 病例和 504853 例对照），以及英国生物库和芬兰基因组中 800 多种其他人类疾病。
使用 IVW-MR，我们在 3 个队列的荟萃分析或每个单独队列中均未发现 Galectin-3 水平与 NAFLD 之间存在因果关系。在进行多次检验校正后，我们未发现 Galectin-3 水平与 >800 个人类疾病相关特征之间存在因果关系。
本 MR 研究未发现循环 Galectin-3 水平与 NAFLD 或任何其他疾病特征之间存在因果关系，表明血浆 Galectin-3 水平可能与 NAFLD 或其他人类疾病的发病机制无直接关系。
