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.