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Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study

CONTEXT: Observational studies indicated obesity and glutamatergic dysfunction as potential risk factors of depression, and reported disturbance of glutamine metabolism in obese state. However, it remains unclear whether the interrelationships between obesity, glutamine, and depression are causal. O...

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Autores principales: He, Ruixin, Zheng, Ruizhi, Zheng, Jie, Li, Mian, Wang, Tiange, Zhao, Zhiyun, Wang, Shuangyuan, Lin, Hong, Lu, Jieli, Chen, Yuhong, Xu, Yu, Wang, Weiqing, Xu, Min, Bi, Yufang, Ning, Guang
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Oxford University Press 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188313/
https://www.ncbi.nlm.nih.gov/pubmed/36510667
http://dx.doi.org/10.1210/clinem/dgac707
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author He, Ruixin
Zheng, Ruizhi
Zheng, Jie
Li, Mian
Wang, Tiange
Zhao, Zhiyun
Wang, Shuangyuan
Lin, Hong
Lu, Jieli
Chen, Yuhong
Xu, Yu
Wang, Weiqing
Xu, Min
Bi, Yufang
Ning, Guang
author_facet He, Ruixin
Zheng, Ruizhi
Zheng, Jie
Li, Mian
Wang, Tiange
Zhao, Zhiyun
Wang, Shuangyuan
Lin, Hong
Lu, Jieli
Chen, Yuhong
Xu, Yu
Wang, Weiqing
Xu, Min
Bi, Yufang
Ning, Guang
author_sort He, Ruixin
collection PubMed
description CONTEXT: Observational studies indicated obesity and glutamatergic dysfunction as potential risk factors of depression, and reported disturbance of glutamine metabolism in obese state. However, it remains unclear whether the interrelationships between obesity, glutamine, and depression are causal. OBJECTIVE: We conducted 2-sample bidirectional mendelian randomization (MR) analyses to explore the causalities between circulating glutamine levels, specific depressive symptoms, major depressive disorder (MDD), and body mass index (BMI). METHODS: Univariable MR, multivariable MR (MVMR), and linkage disequilibrium score regression (LDSR) analyses were performed. RESULTS: Genetic downregulation of glutamine was causally associated with MDD, anhedonia, tiredness, and depressed mood at the false discovery rate (FDR)-controlled significance level (estimate, −0.036 ∼ −0.013; P = .005 to P = .050). Elevated BMI was causally linked to lower glutamine level (estimate, –0.103; P = .037), as well as more severe depressed mood, tiredness, and anhedonia (estimate, 0.017 ∼ 0.050; P < .001 to P = .040). In MVMR analysis, BMI was causally related to depressed mood dependently of glutamine levels. Conversely, it showed limited evidence supporting causal effects of depression on glutamine levels or BMI, except a causal association of tiredness with elevated BMI (estimate, 0.309; P = .003). LDSR estimates were directionally consistent with MR results. CONCLUSION: The present study reported that higher BMI was causally associated with lower glutamine levels. Both obesity and downregulation of glutamine were causally linked to depression.
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spelling pubmed-101883132023-05-18 Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study He, Ruixin Zheng, Ruizhi Zheng, Jie Li, Mian Wang, Tiange Zhao, Zhiyun Wang, Shuangyuan Lin, Hong Lu, Jieli Chen, Yuhong Xu, Yu Wang, Weiqing Xu, Min Bi, Yufang Ning, Guang J Clin Endocrinol Metab Clinical Research Article CONTEXT: Observational studies indicated obesity and glutamatergic dysfunction as potential risk factors of depression, and reported disturbance of glutamine metabolism in obese state. However, it remains unclear whether the interrelationships between obesity, glutamine, and depression are causal. OBJECTIVE: We conducted 2-sample bidirectional mendelian randomization (MR) analyses to explore the causalities between circulating glutamine levels, specific depressive symptoms, major depressive disorder (MDD), and body mass index (BMI). METHODS: Univariable MR, multivariable MR (MVMR), and linkage disequilibrium score regression (LDSR) analyses were performed. RESULTS: Genetic downregulation of glutamine was causally associated with MDD, anhedonia, tiredness, and depressed mood at the false discovery rate (FDR)-controlled significance level (estimate, −0.036 ∼ −0.013; P = .005 to P = .050). Elevated BMI was causally linked to lower glutamine level (estimate, –0.103; P = .037), as well as more severe depressed mood, tiredness, and anhedonia (estimate, 0.017 ∼ 0.050; P < .001 to P = .040). In MVMR analysis, BMI was causally related to depressed mood dependently of glutamine levels. Conversely, it showed limited evidence supporting causal effects of depression on glutamine levels or BMI, except a causal association of tiredness with elevated BMI (estimate, 0.309; P = .003). LDSR estimates were directionally consistent with MR results. CONCLUSION: The present study reported that higher BMI was causally associated with lower glutamine levels. Both obesity and downregulation of glutamine were causally linked to depression. Oxford University Press 2022-12-13 /pmc/articles/PMC10188313/ /pubmed/36510667 http://dx.doi.org/10.1210/clinem/dgac707 Text en © The Author(s) 2022. Published by Oxford University Press on behalf of the Endocrine Society. https://creativecommons.org/licenses/by-nc-nd/4.0/This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial-NoDerivs licence (https://creativecommons.org/licenses/by-nc-nd/4.0/), which permits non-commercial reproduction and distribution of the work, in any medium, provided the original work is not altered or transformed in any way, and that the work is properly cited. For commercial re-use, please contact journals.permissions@oup.com
spellingShingle Clinical Research Article
He, Ruixin
Zheng, Ruizhi
Zheng, Jie
Li, Mian
Wang, Tiange
Zhao, Zhiyun
Wang, Shuangyuan
Lin, Hong
Lu, Jieli
Chen, Yuhong
Xu, Yu
Wang, Weiqing
Xu, Min
Bi, Yufang
Ning, Guang
Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study
title Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study
title_full Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study
title_fullStr Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study
title_full_unstemmed Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study
title_short Causal Association Between Obesity, Circulating Glutamine Levels, and Depression: A Mendelian Randomization Study
title_sort causal association between obesity, circulating glutamine levels, and depression: a mendelian randomization study
topic Clinical Research Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC10188313/
https://www.ncbi.nlm.nih.gov/pubmed/36510667
http://dx.doi.org/10.1210/clinem/dgac707
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