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      Waist-to-hip ratio and nonalcoholic fatty liver disease: a clinical observational and Mendelian randomization analysis

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          Abstract

          Background

          Obesity often coincides with non-alcoholic fatty liver disease (NAFLD), yet a significant portion of NAFLD patients exhibit normal body mass index (BMI) but have abdominal obesity. Recognizing this discrepancy, we aimed to delve deeper into this phenomenon through observational studies coupled with two-sample Mendelian randomization (MR) analysis, with waist-to-hip ratio (WHR) serving as the indicator for abdominal obesity. Our objective was to ascertain whether WHR correlates with an increased risk of NAFLD development.

          Methods

          This study utilized data from the National Health and Nutrition Examination Survey (NHANES) 2017–2018 to examine the association between WHR and NAFLD through weighted multivariate logistic regression models. On this basis, subgroup analyses were performed to further explore the correlation between WHR and NAFLD. Subsequently, a two-sample MR analysis was conducted using genome-wide association studies (GWAS) data to investigate the potential causal relationship between WHR and NAFLD. Sensitivity analyses were also employed to ensure the robustness of our findings.

          Results

          A total of 3,732 eligible participants were included in the analysis. Weighted multivariable-adjusted logistic regression models revealed a positive association between WHR and the risk of NAFLD (Q2vsQ1: OR = 1.94 [95% CI: 1.55–2.44]; Q3vsQ1: OR = 2.08 [95% CI: 1.51–2.85]; Q4vsQ1: OR = 3.70 [95% CI: 2.13–6.43], p < 0.05). The results of the subgroup analysis suggested that there was an interaction in the correlation between WHR and NAFLD in normal weight, overweight, and obese populations ( p < 0.05). The RCS curves indicated that there was a nonlinear relationship between WHR and NAFLD in populations with BMI in the normal versus obese categories. Furthermore, MR analysis provided additional support for the causal relationship between WHR and NAFLD. Using inverse variance weighting (IVW), the MR analysis yielded an OR of 2.062 (95% CI: 1.680–2.531, p<0.05). Consistent results were obtained with the other four MR methods, all supporting the same direction of causality. Sensitivity analyses were performed to assess the robustness of the findings ( p > 0.5), further reinforcing the reliability of the observed associations.

          Conclusion

          WHR elevation heightens the susceptibility to NAFLD.

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          Most cited references42

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          Global burden of NAFLD and NASH: trends, predictions, risk factors and prevention

          NAFLD is one of the most important causes of liver disease worldwide and will probably emerge as the leading cause of end-stage liver disease in the coming decades, with the disease affecting both adults and children. The epidemiology and demographic characteristics of NAFLD vary worldwide, usually parallel to the prevalence of obesity, but a substantial proportion of patients are lean. The large number of patients with NAFLD with potential for progressive liver disease creates challenges for screening, as the diagnosis of NASH necessitates invasive liver biopsy. Furthermore, individuals with NAFLD have a high frequency of metabolic comorbidities and could place a growing strain on health-care systems from their need for management. While awaiting the development effective therapies, this disease warrants the attention of primary care physicians, specialists and health policy makers.
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            Reading Mendelian randomisation studies: a guide, glossary, and checklist for clinicians

            Mendelian randomisation uses genetic variation as a natural experiment to investigate the causal relations between potentially modifiable risk factors and health outcomes in observational data. As with all epidemiological approaches, findings from Mendelian randomisation studies depend on specific assumptions. We provide explanations of the information typically reported in Mendelian randomisation studies that can be used to assess the plausibility of these assumptions and guidance on how to interpret findings from Mendelian randomisation studies in the context of other sources of evidence
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              MAFLD: A consensus-driven proposed nomenclature for metabolic associated fatty liver disease

              Fatty liver associated with metabolic dysfunction is common, affects a quarter of the population, and has no approved drug therapy. Although pharmacotherapies are in development, response rates appear modest. The heterogeneous pathogenesis of metabolic fatty liver diseases and inaccuracies in terminology and definitions necessitate a reappraisal of nomenclature to inform clinical trial design and drug development. A group of experts sought to integrate current understanding of patient heterogeneity captured under the acronym nonalcoholic fatty liver disease (NAFLD) and provide suggestions on terminology that more accurately reflects pathogenesis and can help in patient stratification for management. Experts reached consensus that NAFLD does not reflect current knowledge, and metabolic (dysfunction) associated fatty liver disease "MAFLD" was suggested as a more appropriate overarching term. This opens the door for efforts from the research community to update the nomenclature and subphenotype the disease to accelerate the translational path to new treatments.
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                Author and article information

                Contributors
                URI : https://loop.frontiersin.org/people/2730609/overviewRole: Role:
                Role:
                Role:
                URI : https://loop.frontiersin.org/people/2799205/overviewRole:
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                Journal
                Front Nutr
                Front Nutr
                Front. Nutr.
                Frontiers in Nutrition
                Frontiers Media S.A.
                2296-861X
                01 November 2024
                2024
                : 11
                : 1426749
                Affiliations
                [1] 1The Second Clinical College of Guangzhou University of Chinese Medicine, Guangzhou , Guangdong Province, China
                [2] 2Infectious Disease Department, Guangdong Provincial Hospital of Integrated Traditional Chinese and Western Medicine, Foshan , Guangdong Province, China
                [3] 3Affiliated Guangdong Hospital of Integrated Traditional Chinese and Western Medicine of Guangzhou University of Chinese Medicine, Guangzhou University of Chinese Medicine , Foshan, Guangdong Province, China
                [4] 4The First Clinical Medical College, Guangzhou University of Chinese Medicine , Guangzhou, Guangdong Province, China
                [5] 5Department of Hepatology, Guangdong Province Hospital of Traditional Chinese Medicine, Guangzhou , Guangdong Province, China
                Author notes

                Edited by: Alina Kurylowicz, Mossakowski Medical Research Institute, Polish Academy of Sciences, Poland

                Reviewed by: Xiaolan Lu, Shanghai Pudong Hospital, China

                Jiachen Sun, Dana–Farber Cancer Institute, United States

                *Correspondence: Weining Xie, xwn1219@ 123456qq.com
                Article
                10.3389/fnut.2024.1426749
                11563977
                39555187
                a7459388-f382-44f3-9f3b-7413a0507c1f
                Copyright © 2024 Xie, Hong, Chen, Wang, Zhang and Chi.

                This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) and the copyright owner(s) are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

                History
                : 02 May 2024
                : 08 October 2024
                Page count
                Figures: 6, Tables: 4, Equations: 0, References: 42, Pages: 11, Words: 6103
                Funding
                The author(s) declare that financial support was received for the research, authorship, and/or publication of this article. This study was supported by the GuangDong Basic and Applied Basic Research Foundation (2023A1515140125), the Medical Scientific Research Foundation of Guangdong Province of China (B2021265), and the Foshan Chinese Medicine Immunity Health Science and Technology Innovation Base Fund.
                Categories
                Nutrition
                Original Research
                Custom metadata
                Clinical Nutrition

                non-alcoholic fatty liver disease,waist-to-hip ratio,mendelian randomization analysis,nhanes,clinical observational study

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