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Assessing the joint effects of mitochondrial genes and physical activity on the psychiatric phenotype of subjective well-being based on the UK Biobank data

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Abstract

Subjective well-being (SWB) is an important measure for mental health status. Previous research has shown that physical activity can affect an individual’s well-being, yet the underlying molecular mechanism remains to be clarified. In this study, we aim to evaluate the potential interactions between mitochondrial genes and physical activity (PA) as well as their combined effects on individual well-being. SWB phenotype data in UK Biobank were enrolled for this study including nine aspects such as work/job satisfaction, health satisfaction, family relationship satisfaction, friendships satisfaction, financial situation satisfaction, ever depressed for a whole week, general happiness, general happiness with own health and belief that own life is meaningful. We made analysis for each aspects separately. Firstly, mitochondria-wide association studies (MiWAS) was conducted to assess the association of mitochondrial Single Nucleotide Polymorphisms SNP with each aspect of SWB. Then an interaction analysis of mitochondrial DNA (mtDNA) mutation and PA was performed to evaluate their joint effect on SWB status. Meanwhile, these two analysis were made for female and male group separately as well as the total samples, all under the control of possible confounding factors including gender, age, Townsend Deprivation Index (TDI), education, alcohol consumption, smoking habits, and 10 principal components. MiWAS analysis identified 45 mtSNPs associated with 9 phenotypes of SWB. For example, m.15218A > G on MT-CYB in the health satisfaction phenotype of the total subjects. Gender-specific analyses found 30 mtSNPs in females and 58 in males, involving 13 mtGenes. In mtDNA-PA interaction analysis, we also identified 10 significant mtDNA-PA interaction sets for SWB. For instance, m.13020 T > C (MT-ND5) was associated with the SWB financial situation satisfaction phenotype in all subjects (P = 0.00577). In addition, MiWAS analysis identified 12 mtGene variants associated with SWB, as MT-ND1 and MT-ND2. However, in mtDNA-PA interactions we detected 7 mtDNA affecting psychiatric disorders occurring, as in the friendships satisfaction phenotype (m.3394 T > C on MT-ND1). Our study results suggest an implication of the interaction between mitochondrial function and physical activity in the risk of psychiatric disorder development.

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Data availability

The UK Biobank data are available through the UK Biobank Access Management System https://www.ukbiobank.ac.uk/. We will return the derived data fields following UK Biobank policy; in due course, they will be available through the UK Biobank Access Management System.

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Acknowledgements

This study was conducted using the UK Biobank Resource (Application 46478).

Funding

The National Natural Scientific Foundation of China (82273753, 81922059) and The Natural Science Basic Research Plan in Shaanxi Province of China (2021JCW-08).

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Authors and Affiliations

  1. NHC Key Laboratory of Environment and Endemic Diseases, School of Public Health, Health Science Center, Xi’an Jiaotong University, Xi’an, 710061, China

    Panxing Shi, Bingyi Wang, Sirong Shi, Xiaoge Chu, Chen Liu, Meijuan Kang, Jingni Hui, Yifan Gou, Ruixue Zhou, Ye Liu, Yumeng Jia, Feng Zhang & Yan Wen

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  1. Panxing Shi
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Contributions

Panxing Shi had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis. Yan Wen and Feng Zhang conceptualized and designed the study. All authors contributed in acquisition, analysis, and interpretation of the data. Panxing Shi drafted the manuscript. Yan Wen helped with critical revision of the manuscript for important intellectual content. Yan Wen and Bingyi Wang performed statistical analysis. Yan Wen supervised the study.

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Correspondence to Yan Wen.

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All authors report no biomedical financial interests or potential conflicts of interest.

Institutional review board statement

This study has been approved by UKB (Application 46478) and obtained health-related records of participants.

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Informed consent was obtained from all subjects involved in the study.

Supplementary Information

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406_2024_1822_MOESM1_ESM.docx

Supplementary file1 SWB has nine phenotypes which are work/job satisfaction, health satisfaction, family relationship satisfaction, friendships satisfaction, financial situation satisfaction, ever depressed for a whole week, general happiness, general happiness with own health and belief that own life is meaningful (DOCX 18 KB)

Supplementary file2 (DOCX 15 KB)

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Shi, P., Wang, B., Shi, S. et al. Assessing the joint effects of mitochondrial genes and physical activity on the psychiatric phenotype of subjective well-being based on the UK Biobank data. Eur Arch Psychiatry Clin Neurosci (2024). https://doi.org/10.1007/s00406-024-01822-y

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