Cross‐sectional and Mendelian randomization study of fibroblast growth factor 19 reveals causal associations with metabolic diseases

• Published in: Journal of gastroenterology and hepatology Vol. 39; no. 12; pp. 2872 - 2879
• Main Authors: Li, Yan, Dai, Changyong, Yang, Haiqing, Zeng, Huang, Ruan, Yuhua, Dai, Mingjia, Hao, Jungui, Wang, Liping, Yan, Xuebing, Ji, Fang
• Format: Journal Article
• Language: English
• Published: Australia Wiley Subscription Services, Inc 01.12.2024
• Subjects: Adult; Aspartate aminotransferase; Biomarkers; Biomarkers - blood; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Diseases - epidemiology; Cardiovascular Diseases - etiology; Cardiovascular Diseases - genetics; Cholesterol; Cirrhosis; Cross-Sectional Studies; Diabetes; Diabetes mellitus (non-insulin dependent); Fatty liver; Female; fibroblast growth factor 19; Fibroblast Growth Factors - blood; Fibroblast Growth Factors - genetics; Fibroblasts; Genome-wide association studies; Genome-Wide Association Study; Genomic analysis; Growth factors; Humans; Lipids; Liver cirrhosis; Liver diseases; Male; Mendelian randomization; Mendelian Randomization Analysis; metabolic diseases; Metabolic Diseases - epidemiology; Metabolic Diseases - genetics; Metabolic disorders; Middle Aged; Non-alcoholic Fatty Liver Disease - blood; Non-alcoholic Fatty Liver Disease - genetics; nonalcoholic fatty liver disease; Obesity - genetics; Population studies; Statistical analysis; Triglycerides; nonalcoholic fatty liver disease; Mendelian randomization; metabolic diseases; fibroblast growth factor 19
• DOI: 10.1111/jgh.16687
• ISSN: 0815-9319; 1440-1746

Background and Aim Fibroblast growth factor 19 (FGF19) is an intestinal‐derived factor that plays a role in metabolic diseases. We performed a differential study of circulating FGF19 levels and investigated the causal effects of FGF19 on metabolic diseases using Mendelian randomization (MR). Methods Firstly, 958 subjects were included in the physical examination center of affiliated hospital from January 2019 to January 2021. Dividing the subjects into different subgroups to compare FGF19 levels. We conducted a two‐sample MR analysis of genetically predicted circulating FGF19 in relation to alcohol, cardiovascular and metabolic biomarkers and diseases, and liver function biomarkers using publicly available genome‐wide association study summary statistics data. Results The circulating FGF19 levels in nonalcoholic fatty liver disease (NAFLD) patients were lower than those without NAFLD (P < 0.001). The FGF19 levels in participants with obese were lower than those without obese (P < 0.001). In two‐sample MR analyses, genetically predicted higher circulating FGF19 levels was significantly associated with lower aspartate aminotransferase, γ‐glutamyltransferase, triglycerides, total cholesterol, low‐density lipoprotein, and C‐reactive protein concentrations (P < 0.05) and a negative correlation with cardiovascular disease and cirrhosis whereas a positive association with type 2 diabetes mellitus (P < 0.05). Conclusions Our study found that circulating FGF19 levels were lower in NAFLD and obese populations. Additionally, our MR research results support the causal effects of FGF19 on improved liver function, lipids, and reduced the occurrence of inflammation, cardiovascular disease, and cirrhosis. We found a positive correlation with diabetes, which may indicate a compensatory increase in regulating above FGF19 resistance states in humans.