Mi Jiarui, Liu Zhengye, Jiang Lingjuan, Li Meizi, Wu Xia, Zhao Nan, Wan Ziqi, Bai Xiaoyin, Feng Yunlu
Department of Gastroenterology, Peking Union Medical College Hospital, Peking Union Medical College and Chinese Academy of Medical Sciences, Beijing, China.
Master Programme of Biomedicine, Karolinska Institutet, Stockholm, Sweden.
Front Nutr. 2022 Oct 10;9:1021942. doi: 10.3389/fnut.2022.1021942. eCollection 2022.
There is very limited evidence on the causal effects of blood metabolites on pancreatitis risks. To reveal the causal associations between plasma metabolites and pancreatitis risks, we performed two-sample Mendelian randomization (MR) and Bayesian model averaging (MR-BMA) analyses in European ancestry.
The summary-level statistics from two genome-wide association studies with 249 and 123 metabolic traits derived from two separate cohorts involving ~115,000 (UK Biobank) and ~25,000 individuals from European ancestry were used for the analyses. The summary statistics of four pancreatitis datasets from FinnGen R5 and two pancreatitis datasets from UK Biobank were exploited as the outcome. We first performed univariable MR analysis with different metabolic GWAS data on multiple pancreatitis datasets to demonstrate the association pattern among different metabolites categories. Next, we exploited the MR-BMA method to pinpoint the dominating factors on the increased risk of pancreatitis.
In the primary analysis with 249 traits, we found that plasma triglycerides were positively associated with pancreatitis risk. Intriguingly, a large number of traits associated with saturation or unsaturation of fatty acids also demonstrated causal associations. The replication study analyzing 123 metabolic traits suggested that bisallylic groups levels and omega-3 fatty acids were inversely correlated with pancreatitis risk. MR-BMA analyses indicated that the ratio of triglycerides to total lipid in various HDL particles played leading roles in pancreatitis susceptibility. In addition, the degree of unsaturation, the ratio of polyunsaturated fatty acids to monounsaturated fatty acids and the level of monounsaturated fatty acids showed causal associations with either decreased or increased pancreatitis susceptibility.
Our MR study provided an atlas of causal associations of genetically predicted blood metabolites on pancreatitis, and offered genetic insights showing intervention in triglycerides and the supplementation of unsaturated fatty acids are potential strategies in the primary prevention of pancreatitis.
关于血液代谢物对胰腺炎风险的因果效应的证据非常有限。为了揭示血浆代谢物与胰腺炎风险之间的因果关联，我们在欧洲血统人群中进行了两样本孟德尔随机化（MR）和贝叶斯模型平均（MR-BMA）分析。
来自两项全基因组关联研究的汇总统计数据被用于分析，这两项研究分别涉及约115,000名（英国生物银行）和约25,000名欧洲血统个体的两个独立队列，共得出249个和123个代谢性状。来自芬兰基因库R5的四个胰腺炎数据集和英国生物银行的两个胰腺炎数据集的汇总统计数据被用作结果。我们首先对多个胰腺炎数据集使用不同的代谢全基因组关联研究（GWAS）数据进行单变量MR分析，以展示不同代谢物类别之间的关联模式。接下来，我们利用MR-BMA方法来确定导致胰腺炎风险增加的主要因素。
在对249个性状的初步分析中，我们发现血浆甘油三酯与胰腺炎风险呈正相关。有趣的是，大量与脂肪酸饱和或不饱和相关的性状也显示出因果关联。对123个代谢性状的重复研究表明，双烯丙基基团水平和ω-3脂肪酸与胰腺炎风险呈负相关。MR-BMA分析表明，各种高密度脂蛋白（HDL）颗粒中甘油三酯与总脂质的比率在胰腺炎易感性中起主要作用。此外，不饱和程度、多不饱和脂肪酸与单不饱和脂肪酸的比率以及单不饱和脂肪酸水平与胰腺炎易感性的降低或增加均显示出因果关联。
我们的MR研究提供了一份关于基因预测的血液代谢物与胰腺炎因果关联的图谱，并提供了遗传学见解，表明干预甘油三酯和补充不饱和脂肪酸是胰腺炎一级预防的潜在策略。
