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

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.