摘要
背景:炎症性肠病包括溃疡性结肠炎和克罗恩病,是一种与营养不良、肌肉减少症和疾病严重程度相关的慢性疾病,然而关于它们之间遗传关联及因果关系的研究有限。目的:运用先进的统计遗传学方法系统探究营养、营养状况与炎症性肠病之间的共同遗传基础及因果关系。方法:从GWAS Catalog数据库(由美国国家人类基因组研究所和欧洲生物信息研究所共同构建,系统收录公开发表的基因组关联研究结果)下载矿物质、维生素、白蛋白、血红蛋白、脂肪酸和肌肉减少症特征(四肢瘦体质量和握力)的单核苷酸多态性数据,从R10版本FinnGen数据库(由芬兰国家基因组中心牵头构建的大规模基因组学项目)获取炎症性肠病及其亚型的数据,结合先进的统计遗传学方法,包括连锁不平衡评分回归、跨表型关联分析和孟德尔随机化,来推断营养指标、肌肉减少症与炎症性肠病之间的关联。结果与结论:此研究揭示了显著的遗传相关性:维生素D与炎症性肠病(rg=-0.080,P=0.029)以及溃疡性结肠炎(rg=-0.087,P=0.027)相关;四肢瘦体质量与炎症性肠病(rg=-0.100,P=0.0002)、溃疡性结肠炎(rg=-0.100,P=0.0002)以及小肠型克罗恩病(rg=-0.081,P=0.035)相关;握力与小肠型克罗恩病(rg=-0.125,P=0.035)相关。此外,孟德尔随机化分析表明镁水平与炎症性肠病(OR=1.41,P=0.036)以及小肠型克罗恩病(OR=1.78,P=0.035)之间存在正向因果关系。跨表型关联分析确定了共享的单核苷酸多态性,尤其是在人类白细胞抗原区域内,这些单核苷酸多态性对营养状况和炎症性肠病均有影响。研究结果进一步解释了营养、肌肉减少症和炎症性肠病之间的遗传联系,表明有针对性的营养管理可能是减缓疾病进展的关键。这项研究为提出更个性化的治疗方法提供了新视角,对炎症性肠病的预防策略具有潜在意义。
BACKGROUND:Inflammatory bowel disease,encompassing ulcerative colitis and Crohn’s disease,is a chronic condition linked to malnutrition,sarcopenia,and disease severity,with limited research on their genetic associations.OBJECTIVE:To systematically explore the common genetic basis and causal relationships between nutrition,nutritional status,and inflammatory bowel disease using advanced statistical genetics.METHODS:Single nucleotide polymorphism data for nutritional markers(minerals,vitamins,albumin,hemoglobin,and fatty acids)and sarcopenia traits(appendicular lean mass and grip strength)were obtained from the GWAS Catalog database(jointly established by the National Human Genome Research Institute and the European Bioinformatics Institute,which systematically curates published genome-wide association studies).Summary statistics for inflammatory bowel disease and its subtypes were retrieved from the FinnGen R10 release(a large-scale genomics project coordinated by the Finnish Institute for Health and Welfare).Advanced statistical genetics methods,including linkage disequilibrium score regression,cross-phenotype association analysis,and Mendelian randomization,were applied to infer the associations between nutritional markers,sarcopenia,and inflammatory bowel disease.RESULTS AND CONCLUSION:This study revealed notable genetic correlations:vitamin D with inflammatory bowel disease(rg=-0.080,P=0.029)and ulcerative colitis(rg=-0.087,P=0.027),appendicular lean mass with inflammatory bowel disease(rg=-0.100,P=0.0002),ulcerative colitis(rg=-0.100,P=0.0002),and small intestine Crohn’s disease(rg=-0.081,P=0.035),grip strength with small intestine Crohn’s disease(rg=-0.125,P=0.035).Furthermore,Mendelian randomization analysis demonstrated a positive causal link between magnesium levels and inflammatory bowel disease(OR=1.41,P=0.036),and small intestine Crohn’s disease(OR=1.78,P=0.035).Cross-phenotype association identified shared single nucleotide polymorphisms,particularly within the human leukocyte antigen region,influencing both nutritional status and inflammatory bowel disease.Our findings advanced the understanding of genetic connections between nutrition,sarcopenia,and inflammatory bowel disease,suggesting that targeted nutritional management may be key in mitigating disease progression.This research paves the way for more personalized treatment approaches,with potential implications for preventive strategies in inflammatory bowel disease care.
作者
廖桂彬
吴一璇
汤璟
黄金科
王俊
严梓萁
刘书君
张海燕
Liao Guibin;Wu Yixuan;Tang Jing;Huang Jinke;Wang Jun;Yan Ziqi;Liu Shujun;Zhang Haiyan(The Second Affiliated Hospital of Guangzhou University of Chinese Medicine(Guangdong Provincial Hospital of Chinese Medicine),Guangzhou 510006,Guangdong Province,China;The First Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China;The Second Clinical Medical College,Guangzhou University of Chinese Medicine,Guangzhou 510405,Guangdong Province,China;Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome,Guangzhou 510120,Guangdong Province,China)
出处
《中国组织工程研究》
北大核心
2026年第22期5876-5885,共10页
Chinese Journal of Tissue Engineering Research
基金
广东省中医证候临床研究重点实验室项目(2023KT15486),项目负责人:张海燕
国家中医药管理局项目(ZDYN-2024-A-079),项目负责人:张海燕
国家自然科学基金项目(82400635),项目负责人:王俊。
关键词
营养
肌肉减少症
炎症性肠病
全基因组关联研究
欧洲生物信息研究所
芬兰基因组项目
连锁不平衡评分回归
跨表型关联分析
孟德尔随机化
nutrition
sarcopenia
inflammatory bowel disease
genome-wide association study
European Bioinformatics Institute
FinnGen Project
linkage disequilibrium score regression
cross-phenotype association analysis
Mendelian randomization
