Associations between gut microbiota and hand grip strength: a polygenetic scoring analysis and genome-wide environmental interaction study

Abstract

Background We aim to explore the genetic association between hand grip strength (HGS) and gut microbiota (GM). Methods The genome-wide association study (GWAS) data of GM was obtained from a recently published study, involving 2,646 individuals. Phenotypic data of left HGS (n = 375,229) and right HGS (n = 375,279) were derived from the UK Biobank. Firstly, PLINK 2.0 was used to calculate 114 GM related polygenetic risk score (PRS) of each subject based on GWAS result. Regression analysis was then conducted to evaluate the possible association of GM-PRS and HGS. Then genome-wide by environment interaction study (GWEIS) of GM related traits was then performed using a regression model adjusted for age, gender, BMI and 10 principal components. Results For PRS analysis, 13 candidate GM were identified to be associated with left HGS (P < 0.05), including G_Bifidobacterium (P = 8.36 × 10− 4), G_Clostridium_sensu_stricto (P = 2.69 × 10− 3), and 10 significant GM for right HGS, such as G_Acidaminococcus (P = 1.29 × 10− 2), G_Streptococcus (P = 1.79 × 10− 2). In addition, 4 GM were found to be overlapped in association with both left and right HGS, including G_Bifidobacterium (P right HGS = 2.78 × 10− 2, P left HGS = 8.36 × 10− 4). Furthermore, several genome-wide significant GWEIS associations were detected for HGS, including 3 significant SNPs interacted with G_Butyricicoccus (P < 5 × 10− 8) for right HGS (rs41310432, P = 3.86 × 10− 8; closest gene: NASP; rs1053941, P = 4.71 × 10− 8; closest gene: NASP; rs6671239, P = 4.73 × 10− 8, closest gene: GPBP1L1), and 1 suggestive intronic SNP in CACNA1H on chromosome 16 interacted with G_Butyricicoccus (rs139206507, P = 8.68 × 10− 8 ) for left HGS. Conclusions Our study holds great potential gaining a better understanding of the relationship between GM and HGS.