Department of Digital Health, Samsung Advanced Institute for Health Sciences & Technology (SAIHST), Sungkyunkwan University, Samsung Medical Center, Seoul, Republic of Korea.
Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Republic of Korea.
Obesity (Silver Spring). 2023 May;31(5):1436-1444. doi: 10.1002/oby.23722. Epub 2023 Apr 4.
Although the association between adiposity and gastrointestinal (GI) diseases has been explored, the causal effects of adiposity on GI diseases are largely unknown.
Mendelian randomization was conducted using single-nucleotide polymorphisms associated with BMI and waist circumference (WC) as instrumental variables, and the causal associations of BMI or WC with GI conditions were estimated among >400,000 UK Biobank participants, >170,000 Finnish-descent participants, and numerous consortia participants of predominantly European ancestry.
Genetically predicted BMI was robustly associated with increased risk of nonalcoholic fatty liver disease (NAFLD), cholecystitis, cholelithiasis, and primary biliary cholangitis. For the diseases, the odds ratio per 1-SD increase in genetically predicted BMI (4.77 kg/m ) ranged from 1.22 (95% CI: 1.12-1.34; p < 0.0001) for NAFLD to 1.65 (95% CI: 1.31-2.06; p < 0.0001) for cholecystitis. Genetically predicted WC was robustly associated with increased risk of NAFLD, alcoholic liver disease, cholecystitis, cholelithiasis, colon cancer, and gastric cancer. Alcoholic liver disease was consistently associated with WC even after adjusting for alcohol consumption in a multivariable Mendelian randomization analysis. The odds ratio per 1-SD increase in genetically predicted WC (12.52 cm) for such associations ranged from 1.41 (95% CI: 1.17-1.70; p = 0.0015) for gastric cancer to 1.74 (95% CI: 1.21-1.78; p < 0.0001) for cholelithiasis.
High genetically predicted adiposity was causally associated with an increased risk of GI abnormalities, particularly of hepatobiliary organs (liver, biliary tract, and gallbladder) that are functionally related to fat metabolism.
尽管肥胖与胃肠道（GI）疾病之间的关联已被探讨，但肥胖对 GI 疾病的因果影响在很大程度上仍是未知的。
使用与 BMI 和腰围（WC）相关的单核苷酸多态性作为工具变量进行孟德尔随机化，在超过 40 万名英国生物银行参与者、超过 17 万芬兰裔参与者以及众多主要为欧洲血统的联盟参与者中，估计 BMI 或 WC 与 GI 疾病的因果关联。
遗传预测的 BMI 与非酒精性脂肪性肝病（NAFLD）、胆囊炎、胆石症和原发性胆汁性胆管炎的风险增加密切相关。对于这些疾病，遗传预测 BMI 每增加 1-SD 的优势比（4.77kg/m）范围从 NAFLD 的 1.22（95%CI：1.12-1.34；p<0.0001）到胆囊炎的 1.65（95%CI：1.31-2.06；p<0.0001）。遗传预测的 WC 与 NAFLD、酒精性肝病、胆囊炎、胆石症、结肠癌和胃癌的风险增加密切相关。即使在多变量孟德尔随机化分析中调整饮酒量后，酒精性肝病仍与 WC 相关。遗传预测 WC 每增加 1-SD（12.52cm）的比值比（OR）范围从胃癌的 1.41（95%CI：1.17-1.70；p=0.0015）到胆石症的 1.74（95%CI：1.21-1.78；p<0.0001）。
高遗传预测的肥胖与 GI 异常的风险增加密切相关，特别是与脂肪代谢功能相关的肝胆器官（肝脏、胆道和胆囊）异常。
