To explore the causal association between the serum lipid profile and inflammatory bowel disease using bidirectional Mendelian randomisation analysis

Xiaoli Pang, Huizhong Yang, Mingyu Li, Mayte Suárez-Fariñas, Suyan Tian
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Abstract

Despite studies confirming that patients with inflammatory bowel disease (IBD) present with dyslipidaemia, the associations between IBD and the serum lipid profile have not been determined. The present study aimed to investigate the causal relationship between the serum lipid profile and IBD risk and elucidate the nature of the interactions between them.Two-sample Mendelian randomisation (MR) analysis was performed to investigate the causal links between total cholesterol (TC), total triglyceride (TG), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), apolipoprotein A (Apo A), apolipoprotein B (Apo B) and lipoprotein (a) (Lp(a)) and IBD. The study was carried out using the R TwoSampleMR and Mendelian randomisation packages.All MR methods, including the weighted median, weighted mode, inverse-variance weighted model, MR-PRESSO, contamination mixture and MR Egger, supported a null causal relationship between TG, TC, HDL-C, LDL-C, Apo A, Apo B and Lp(a) and between IBD, Crohn’s disease and ulcerative colitis. Null causal effects of lipid indices on IBD were validated through independent genome-wide association studies (GWAS), indicating that the findings are robust.Our findings suggest that none of the seven lipid indices may be a potential risk factor for the onset of IBD. However, additional research is needed since our MR analyses cannot assess the potential non-linear causal relationship between serum lipids and IBD.
利用双向孟德尔随机分析法探讨血清脂质状况与炎症性肠病之间的因果关系
尽管研究证实炎症性肠病(IBD)患者会出现血脂异常,但 IBD 与血清脂质谱之间的关系尚未确定。本研究旨在调查血清脂质谱与 IBD 风险之间的因果关系,并阐明两者之间相互作用的性质。研究采用双样本孟德尔随机化(MR)分析方法,探讨总胆固醇(TC)、总甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、载脂蛋白A(载脂蛋白A)、载脂蛋白B(载脂蛋白B)和脂蛋白(a)(Lp(a))与IBD之间的因果关系。所有 MR 方法(包括加权中位数、加权模式、逆方差加权模型、MR-PRESSO、污染混合物和 MR Egger)都支持 TG、TC、HDL-C、LDL-C、载脂蛋白 A、载脂蛋白 B 和 Lp(a) 与 IBD、克罗恩病和溃疡性结肠炎之间的因果关系为空。通过独立的全基因组关联研究(GWAS)验证了血脂指数对 IBD 的零因果效应,表明研究结果是可靠的。然而,由于我们的 MR 分析无法评估血清脂质与 IBD 之间潜在的非线性因果关系,因此还需要进行更多的研究。
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