Dalian Medical University, Dalian, Liaoning Province, China.
Department of Gastroenterology, Affiliated Hospital of Yangzhou University, Yangzhou University, No. 368, Hanjiang Middle Road, Hanjiang District, Yangzhou, Jiangsu Province, China.
BMC Endocr Disord. 2024 Mar 20;24(1):40. doi: 10.1186/s12902-024-01569-6.
Previous observational studies have revealed a potential link between non-alcoholic fatty liver disease (NAFLD) and gestational diabetes mellitus (GDM), but their causal relationship remains unclear. Thus, this study aimed to examine whether a causal link exists between genetically determined NAFLD and GDM.
Utilizing publicly accessible genome-wide association studies (GWAS), a two-sample bidirectional Mendelian randomization (MR) analysis was conducted. The GWASs data pertaining to NAFLD and GDM were obtained from the UK Biobank Consortium and FinnGen database in primary analysis, respectively. The random-effects inverse variance weighted (IVW) method was utilized as primary analysis method. Several sensitivity analyses were utilized to verify the robustness of the results. Additionally, we also analyzed the causal effect of potential shared influencing factors on these two conditions.
The result of the IVW method showed that there was no significant causal relationship between genetically determined NAFLD and GDM (OR = 0.98, 95% CI: 0.90-1.07, P = 0.691). Similarly, our reverse MR analysis failed to detect a significant causal effect of GDM on NAFLD (OR = 1.14, 95% CI: 0.97-1.36, P = 0.118). Sensitivity analyses further confirmed the robustness of the results. Moreover, we found that genetically determined body mass index, waist-to-hip ratio, triglycerides, and television viewing time may be positively correlated with NAFLD and GDM, while high-density lipoprotein cholesterol and apolipoprotein A-I may both be negatively correlated with NAFLD and GDM.
The current bidirectional MR study failed to provide sufficient genetic evidence for the causal relationship between NAFLD and GDM.
先前的观察性研究表明，非酒精性脂肪性肝病（NAFLD）与妊娠糖尿病（GDM）之间可能存在关联，但它们之间的因果关系尚不清楚。因此，本研究旨在探讨遗传相关性 NAFLD 与 GDM 之间是否存在因果关系。
利用公开可得的全基因组关联研究（GWAS），进行了两样本双向孟德尔随机化（MR）分析。在主要分析中，分别从英国生物库联盟和芬兰遗传研究中获取了与 NAFLD 和 GDM 相关的 GWAS 数据。主要分析方法采用随机效应逆方差加权（IVW）法。还进行了几种敏感性分析以验证结果的稳健性。此外，我们还分析了这些两种情况的潜在共同影响因素的因果效应。
IVW 方法的结果表明，遗传相关性 NAFLD 与 GDM 之间不存在显著的因果关系（OR=0.98，95%CI：0.90-1.07，P=0.691）。同样，我们的反向 MR 分析也未能检测到 GDM 对 NAFLD 有显著的因果作用（OR=1.14，95%CI：0.97-1.36，P=0.118）。敏感性分析进一步证实了结果的稳健性。此外，我们发现遗传相关性体重指数、腰臀比、甘油三酯和看电视时间可能与 NAFLD 和 GDM 呈正相关，而高密度脂蛋白胆固醇和载脂蛋白 A-I 可能与 NAFLD 和 GDM 均呈负相关。
本双向 MR 研究未能提供足够的遗传证据支持 NAFLD 与 GDM 之间的因果关系。
