Chen Xingdong's team systematically analyzed the causal association between NAFLD and 34 extrahepatic diseases

Recently, the internationally renowned magazine "Metabolism" published the research paper of Chen Xingdong's young researcher team of our institute "Dissecting causal relationships between nonalcoholic fatty liver disease proxied by chronically elevated alanine.
" transaminase levels and 34 extrahepatic diseases”
。 The study used the Mendelian randomization framework system to study the causal association
of nonalcoholic fatty liver disease (NAFLD) with 34 extrahepatic diseases.

NAFLD is a common chronic liver disease
in the population.
With the change of lifestyle, the incidence of metabolic syndromes such as obesity and diabetes continues to increase, and the prevalence of NAFLD in recent years has also shown a rapid upward trend, and the prevalence of NAFLD in China is currently about 30%, and even more than 40%
of urban residents.
NAFLD is not only a clear cause of end-stage liver diseases such as cirrhosis and liver cancer, but previous epidemiological studies have also suggested that NAFLD can significantly increase the risk
of common chronic diseases such as cardiovascular disease, chronic kidney disease, and extrahepatic tumors.
But it is not clear whether NAFLD is one of the "causes" of these diseases or merely an accompanying condition
in the course of their development.
In response to this problem, Chen Xingdong's team used the summarized data of GWAS to construct a Mendelian randomization analysis framework to systematically analyze the causal association
between NAFLD and 34 common extrahepatic diseases.

The researchers first identified 34 chronic extrahepatic diseases in the population that were significantly associated with NAFLD through a literature search, and retrieved the GWAS pooled data for these diseases through an online public data
platform.
On this basis, a Mendelian randomization analysis process (Figure 1) is constructed to ensure the robustness
of the analysis results.

Figure 1.
Mendelian randomization analysis framework

In order to screen for qualified instrumental variables, the researchers conducted three rounds of Mendelian randomization analysis and found a significant and robust causal association between NAFLD and nine diseases, including type 2 diabetes, hypertension, myocardial infarction, and Alzheimer's disease (Figure 2).

Different Mendelian randomization methods are highly consistent in the direction of study estimates (Figure 3).

To further ensure the robustness of the results, the researchers performed a series of sensitivity analyses simultaneously, yielding results
that were very close to the main analysis.

Figure 2.
Association of NAFLD with extrahepatic disease

Figure 3.
Scatterplot of NAFLD association with 9 extrahepatic diseases

Overall, this study provides evidence for the causal association of NAFLD with a variety of extrahepatic diseases, further emphasizing the importance of
NAFLD prevention and management in clinical and public health practice.
Postdoctoral fellow Liu Zhenqiu of the Institute of Human Phenome is the first author of this paper, and young researcher Chen Xingdong is the corresponding author
.
The study was also guided
by Professor Jin Li.
The research was supported
by the Boxin Program, the China Postdoctoral Science Foundation, the National Natural Science Foundation of China, and the National Key Research and Development Program of China.

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