Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study
BackgroundOsteoporosis (OP) is a systemic skeletal disease characterized by compromised bone strength leading to an increased risk of fracture. There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of OP....
| Main Authors: | , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2023-12-01
|
| Series: | Frontiers in Endocrinology |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/articles/10.3389/fendo.2023.1283739/full |
| _version_ | 1797393424849043456 |
|---|---|
| author | Yue Zhou Yunzhi Ni Zhihong Wang Gerald J. Prud’homme Qinghua Wang |
| author_facet | Yue Zhou Yunzhi Ni Zhihong Wang Gerald J. Prud’homme Qinghua Wang |
| author_sort | Yue Zhou |
| collection | DOAJ |
| description | BackgroundOsteoporosis (OP) is a systemic skeletal disease characterized by compromised bone strength leading to an increased risk of fracture. There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of OP. The aim of this study was to assess the causal association between NAFLD and OP.MethodsWe performed two‐sample Mendelian randomization (MR) analyses to investigate the causal association between genetically predicted NAFLD [i.e., imaging‐based liver fat content (LFC), chronically elevated serum alanine aminotransferase (cALT) and biopsy-confirmed NAFLD] and risk of OP. The inverse variant weighted method was performed as main analysis to obtain the causal estimates.ResultsImaging-based LFC and biopsy-confirmed NAFLD demonstrated a suggestive causal association with OP ([odds ratio (OR): 1.003, 95% CI: 1.001-1.004, P < 0.001; OR: 1.001, 95% CI: 1.000-1.002, P = 0.031]). The association between cALT and OP showed a similar direction, but was not statistically significant (OR: 1.001, 95% CI: 1.000-1.002, P = 0.079). Repeated analyses after exclusion of genes associated with confounding factors showed consistent results. Sensitivity analysis indicated low heterogeneity, high reliability and low pleiotropy of the causal estimates.ConclusionThe two‐sample MR analyses suggest a causal association between genetically predicted NAFLD and OP. |
| first_indexed | 2024-03-09T00:03:21Z |
| format | Article |
| id | doaj.art-c4127a0cedb34e8c8e8c3abbbcd4f84a |
| institution | Directory Open Access Journal |
| issn | 1664-2392 |
| language | English |
| last_indexed | 2024-03-09T00:03:21Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Endocrinology |
| spelling | doaj.art-c4127a0cedb34e8c8e8c3abbbcd4f84a2023-12-12T15:26:07ZengFrontiers Media S.A.Frontiers in Endocrinology1664-23922023-12-011410.3389/fendo.2023.12837391283739Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization studyYue Zhou0Yunzhi Ni1Zhihong Wang2Gerald J. Prud’homme3Qinghua Wang4Department of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, ChinaDepartment of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, ChinaDepartment of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, CanadaDepartment of Endocrinology and Metabolism, Huashan Hospital, Shanghai Medical School, Fudan University, Shanghai, ChinaBackgroundOsteoporosis (OP) is a systemic skeletal disease characterized by compromised bone strength leading to an increased risk of fracture. There is an ongoing debate on whether non-alcoholic fatty liver disease (NAFLD) is an active contributor or an innocent bystander in the pathogenesis of OP. The aim of this study was to assess the causal association between NAFLD and OP.MethodsWe performed two‐sample Mendelian randomization (MR) analyses to investigate the causal association between genetically predicted NAFLD [i.e., imaging‐based liver fat content (LFC), chronically elevated serum alanine aminotransferase (cALT) and biopsy-confirmed NAFLD] and risk of OP. The inverse variant weighted method was performed as main analysis to obtain the causal estimates.ResultsImaging-based LFC and biopsy-confirmed NAFLD demonstrated a suggestive causal association with OP ([odds ratio (OR): 1.003, 95% CI: 1.001-1.004, P < 0.001; OR: 1.001, 95% CI: 1.000-1.002, P = 0.031]). The association between cALT and OP showed a similar direction, but was not statistically significant (OR: 1.001, 95% CI: 1.000-1.002, P = 0.079). Repeated analyses after exclusion of genes associated with confounding factors showed consistent results. Sensitivity analysis indicated low heterogeneity, high reliability and low pleiotropy of the causal estimates.ConclusionThe two‐sample MR analyses suggest a causal association between genetically predicted NAFLD and OP.https://www.frontiersin.org/articles/10.3389/fendo.2023.1283739/fullMendelian randomizationcausalitynon-alcoholic fatty liver diseaseliver fat contentosteoporosis |
| spellingShingle | Yue Zhou Yunzhi Ni Zhihong Wang Gerald J. Prud’homme Qinghua Wang Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study Frontiers in Endocrinology Mendelian randomization causality non-alcoholic fatty liver disease liver fat content osteoporosis |
| title | Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study |
| title_full | Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study |
| title_fullStr | Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study |
| title_full_unstemmed | Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study |
| title_short | Causal effects of non-alcoholic fatty liver disease on osteoporosis: a Mendelian randomization study |
| title_sort | causal effects of non alcoholic fatty liver disease on osteoporosis a mendelian randomization study |
| topic | Mendelian randomization causality non-alcoholic fatty liver disease liver fat content osteoporosis |
| url | https://www.frontiersin.org/articles/10.3389/fendo.2023.1283739/full |
| work_keys_str_mv | AT yuezhou causaleffectsofnonalcoholicfattyliverdiseaseonosteoporosisamendelianrandomizationstudy AT yunzhini causaleffectsofnonalcoholicfattyliverdiseaseonosteoporosisamendelianrandomizationstudy AT zhihongwang causaleffectsofnonalcoholicfattyliverdiseaseonosteoporosisamendelianrandomizationstudy AT geraldjprudhomme causaleffectsofnonalcoholicfattyliverdiseaseonosteoporosisamendelianrandomizationstudy AT qinghuawang causaleffectsofnonalcoholicfattyliverdiseaseonosteoporosisamendelianrandomizationstudy |