Introduction
Hand grip strength (HGS), as one of the simplest and least complicated of instrumented muscle strength measures, is showed to reflect overall muscle strength1. Decreased muscle strength and functionality are common and complex changes related to ageing and could affect the function of daily life and survival activities, which increases personal and societal costs 2. The measurement of HGS is simple and reliable and it is related to the function of daily life and survival activities. Therefore, HGS has been used as a significant predictor and biomarker of overall health of individual, not only in the elderly, but also in middle-aged and young people. A number of studies have demonstrated the predictive role of HGS in complicated diseases and traits. For example, Firth et al. reported significant positive associations between maximal HGS and improved cognitive performance in people with major depression and bipolar disorder3. Leong et al.4 performed a prospective epidemiology study including 7 countries and showed that HGS predicted not only all-cause mortality but also cardiovascular mortality, non-cardiovascular mortality, cardiovascular disease occurrence and stroke. In addition, the associations between HGS and mortality were observed not only in older but also in middle-aged and young adults4. Given the reliable and accuracy of HGS as an indicator of general health and nutritional status, we use HGS as a biomarker for overall health of individual in this study.
The heritability of grip strength estimated by Finkel et al. was approximately 75% in men and 47 % in women 5. Sara et al. performed a large-scale genome-wide association study (GWAS) analysis and reported 16 loci associated with grip strength containing genes implicated in structure and function of skeletal muscle fibers, neuronal maintenance and signal transduction, or psychomotor impairment6. What’s more, Inge et al. 7observed a significant gene-environment (G×E) interaction effect on grip trajectories, suggesting that in addition to genetic factors, G×E interactions also influence HGS. While the effects of genetics and G×E interactions on HGS have been proved, the extent and mechanisms of their effects are still unclear.
Cesarean section (C-section) is a lifesaving procedure when delivery is obstructed, or the fetus is in poor condition, and is effective in reducing neonatal and maternal mortality 8. The rate of C-section has increased more than 3-fold worldwide during the past 30 years 8. It is of concern that C-section have been shown to have potential long-term health implications on offspring. C-section could lead to negative health outcomes including allergies9, asthma9, and metabolic abnormalities10. C-section, act as an environment risk factor, might disturb immune activation in offspring by reducing hypothalamus-pituitary-adrenal axis activation 11, and alter the bacterial colonization through the lack of exposure to maternal bowel flora 12. While growing evidence suggests that C-section related to child health, less study have assessed its effect on the overall health status of offspring.
Genome-wide by environmental interaction study (GWEIS) is a method taking into account the role of G×E interaction. G×E interaction indicates the effect due to a mixture of environmental factors and genetic factors, playing an important role in identifying the mechanism of a lot of complex traits and diseases 13. In contrast to GWAS, GWEIS included genome-wide data rather than candidate genes, which significantly improved the ability to detect genotype-phenotype associations missed in GWAS 14.
In this study, we aimed to assess whether C-section constitutes a Gene× C-section interaction with genetic factors and thereby affecting HGS in offspring. Observational analyses followed by GWEIS were performed using individual phenotype and genotype data from UK Biobank. Then we performed gene-set enrichment analysis using FUMA platform. Our study holds potential for clarifying the functional relevance of C-section with HGS.