Yinshi Su, Shuangzhe Lin, Ling She, Jingping Xiong, Yongnian Ding, Yan Zhang, Yuanwen Chen
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Instrumental variables from genome-wide association studies were applied, and initial associations were examined using linkage disequilibrium score (LDSC) regression analysis. Furthermore, mediation analysis was conducted to identify potential mediators. <b>Results:</b> The MR analysis revealed significant positive associations between NAFLD occurrence and major depression (odds ratio [OR] = 1.294, <i>p</i> = 0.003), bipolar disorder (OR = 0.895, <i>p</i> = 0.004), and autism (OR = 1.118, <i>p</i> = 0.005). However, only the putative causal association of major depression on NAFLD remained statistically significant in further validation, including MR-CAUSE and sensitivity analyses, and was not attributable to linkage disequilibrium. No causal effect of NAFLD on mental disorders was found in reverse MR analysis. In LDSC regression, significant positive associations with NAFLD occurrence were observed for major depression (Rg = 0.538, <i>p</i> = 1.36<i>E</i> - 07), ADHD (Rg = 0.798, <i>p</i> = 1.10<i>E</i> - 08), and PTSD (Rg = 0.579, <i>p</i> = 0.009). Mediation analysis identified body mass index (39.33%, <i>p</i> = 0.017), waist-to-hip ratio (8.09%, <i>p</i> = 0.026), triglycerides (39.33%, <i>p</i> = 0.017), and serum concentration of large very low-density lipoprotein (VLDL) particles (8.76%, <i>p</i> = 0.032) as mediators of the causal effect of major depression on NAFLD occurrence. <b>Conclusion:</b> This study suggests a potential causal link between major depression and the development of NAFLD, underscoring the importance of considering major depression in the management of NAFLD patients.</p>","PeriodicalId":48755,"journal":{"name":"Canadian Journal of Gastroenterology and Hepatology","volume":"2025 ","pages":"6632867"},"PeriodicalIF":2.3000,"publicationDate":"2025-08-30","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12407292/pdf/","citationCount":"0","resultStr":"{\"title\":\"Major Depression as a Catalyst for Nonalcoholic Fatty Liver Disease: Insights From a Comprehensive Mendelian Randomization Study.\",\"authors\":\"Yinshi Su, Shuangzhe Lin, Ling She, Jingping Xiong, Yongnian Ding, Yan Zhang, Yuanwen Chen\",\"doi\":\"10.1155/cjgh/6632867\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><p><b>Background:</b> This study aimed to investigate the causal association between mental disorders and nonalcoholic fatty liver disease (NAFLD; now termed metabolic dysfunction-associated steatotic liver disease, MASLD) using Mendelian randomization (MR). <b>Methods:</b> A bidirectional two-sample MR approach was employed to evaluate the causal relationship between NAFLD and eight mental disorders: major depression, anxiety, bipolar disorder, schizophrenia, autism, post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), and eating disorders. The inverse-variance weighted (IVW) method was utilized to estimate causal effects, supported by MR-CAUSE and other sensitivity analyses to address pleiotropy and heterogeneity. Instrumental variables from genome-wide association studies were applied, and initial associations were examined using linkage disequilibrium score (LDSC) regression analysis. Furthermore, mediation analysis was conducted to identify potential mediators. <b>Results:</b> The MR analysis revealed significant positive associations between NAFLD occurrence and major depression (odds ratio [OR] = 1.294, <i>p</i> = 0.003), bipolar disorder (OR = 0.895, <i>p</i> = 0.004), and autism (OR = 1.118, <i>p</i> = 0.005). However, only the putative causal association of major depression on NAFLD remained statistically significant in further validation, including MR-CAUSE and sensitivity analyses, and was not attributable to linkage disequilibrium. No causal effect of NAFLD on mental disorders was found in reverse MR analysis. In LDSC regression, significant positive associations with NAFLD occurrence were observed for major depression (Rg = 0.538, <i>p</i> = 1.36<i>E</i> - 07), ADHD (Rg = 0.798, <i>p</i> = 1.10<i>E</i> - 08), and PTSD (Rg = 0.579, <i>p</i> = 0.009). 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引用次数: 0
摘要
背景:本研究旨在利用孟德尔随机化(MR)研究精神障碍与非酒精性脂肪性肝病(NAFLD,现称为代谢功能障碍相关脂肪性肝病,MASLD)之间的因果关系。方法:采用双向双样本MR方法评估NAFLD与8种精神障碍的因果关系:重度抑郁、焦虑、双相情感障碍、精神分裂症、自闭症、创伤后应激障碍(PTSD)、注意缺陷多动障碍(ADHD)和饮食障碍。利用反方差加权(IVW)方法估计因果效应,并通过MR-CAUSE和其他敏感性分析来解决多效性和异质性问题。应用全基因组关联研究中的工具变量,并使用连锁不平衡评分(LDSC)回归分析来检验初始关联。此外,还进行了中介分析,以确定潜在的中介。结果:磁共振分析显示NAFLD的发生与重度抑郁症(比值比[OR] = 1.294, p = 0.003)、双相情感障碍(比值比[OR] = 0.895, p = 0.004)、自闭症(比值比[OR] = 1.118, p = 0.005)呈正相关。然而,在进一步的验证中,包括MR-CAUSE和敏感性分析,只有假定的重度抑郁与NAFLD的因果关系仍然具有统计学意义,并且不能归因于连锁不平衡。反向MR分析未发现NAFLD与精神障碍的因果关系。在LDSC回归中,重度抑郁症(Rg = 0.538, p = 1.36E - 07)、ADHD (Rg = 0.798, p = 1.10E - 08)和PTSD (Rg = 0.579, p = 0.009)与NAFLD的发生呈显著正相关。中介分析发现体重指数(39.33%,p = 0.017)、腰臀比(8.09%,p = 0.026)、甘油三酯(39.33%,p = 0.017)和血清大极低密度脂蛋白(VLDL)颗粒浓度(8.76%,p = 0.032)是重度抑郁对NAFLD发生因果关系的中介因子。结论:本研究提示重度抑郁与NAFLD的发展之间存在潜在的因果关系,强调了在NAFLD患者的管理中考虑重度抑郁的重要性。
Major Depression as a Catalyst for Nonalcoholic Fatty Liver Disease: Insights From a Comprehensive Mendelian Randomization Study.
Background: This study aimed to investigate the causal association between mental disorders and nonalcoholic fatty liver disease (NAFLD; now termed metabolic dysfunction-associated steatotic liver disease, MASLD) using Mendelian randomization (MR). Methods: A bidirectional two-sample MR approach was employed to evaluate the causal relationship between NAFLD and eight mental disorders: major depression, anxiety, bipolar disorder, schizophrenia, autism, post-traumatic stress disorder (PTSD), attention deficit hyperactivity disorder (ADHD), and eating disorders. The inverse-variance weighted (IVW) method was utilized to estimate causal effects, supported by MR-CAUSE and other sensitivity analyses to address pleiotropy and heterogeneity. Instrumental variables from genome-wide association studies were applied, and initial associations were examined using linkage disequilibrium score (LDSC) regression analysis. Furthermore, mediation analysis was conducted to identify potential mediators. Results: The MR analysis revealed significant positive associations between NAFLD occurrence and major depression (odds ratio [OR] = 1.294, p = 0.003), bipolar disorder (OR = 0.895, p = 0.004), and autism (OR = 1.118, p = 0.005). However, only the putative causal association of major depression on NAFLD remained statistically significant in further validation, including MR-CAUSE and sensitivity analyses, and was not attributable to linkage disequilibrium. No causal effect of NAFLD on mental disorders was found in reverse MR analysis. In LDSC regression, significant positive associations with NAFLD occurrence were observed for major depression (Rg = 0.538, p = 1.36E - 07), ADHD (Rg = 0.798, p = 1.10E - 08), and PTSD (Rg = 0.579, p = 0.009). Mediation analysis identified body mass index (39.33%, p = 0.017), waist-to-hip ratio (8.09%, p = 0.026), triglycerides (39.33%, p = 0.017), and serum concentration of large very low-density lipoprotein (VLDL) particles (8.76%, p = 0.032) as mediators of the causal effect of major depression on NAFLD occurrence. Conclusion: This study suggests a potential causal link between major depression and the development of NAFLD, underscoring the importance of considering major depression in the management of NAFLD patients.
期刊介绍:
Canadian Journal of Gastroenterology and Hepatology is a peer-reviewed, open access journal that publishes original research articles, review articles, and clinical studies in all areas of gastroenterology and liver disease - medicine and surgery.
The Canadian Journal of Gastroenterology and Hepatology is sponsored by the Canadian Association of Gastroenterology and the Canadian Association for the Study of the Liver.