Background Previous observational studies have shown that handgrip strength was inversely associated with gastroesophageal reflux disease (GERD), but the causal relationship is unknown. We aimed to explore the potential causal associations between handgrip strength and GERD by two-sample Mendelian randomization (MR) analyses in European populations.

Methods We obtained publicly available summarized genome-wide association studies data on the left (461,026 participants) and right handgrip strength (461,089 participants) from United Kingdom Biobank, and collected GERD data from a genome meta-analysis (129,080 cases and 473,524 controls). Single-nucleotide polymorphisms (SNPs) met the following criteria were selected as instrumental variables: (1) were significantly associated with exposures (P<5*10^-8); (2) were independent (linkage disequilibrium-r² less than 0.001 within 10,000 kilobases); (3) had a ≥5% effect allele frequency (EAF); and (4) were not palindromic SNPs (A/T or C/G) with EAFs of 40-70%. Finally, 67 and 70 SNPs were used for left and right handgrip strength, respectively. The inverse-variance weighted (IVW) approach was used as the primary approach to calculate the odds ratios (ORs) and 95% confidence intervals (95% CIs) of per standard deviation handgrip strength increase. MR Egger, weighted median, and weighted mode were also applied to test the robustness of the main results.

Results Genetically predicted left handgrip strength was inversely associated with GERD with an OR_IVW (95% CI) of 0.67 (0.54, 0.82) (P<0.001). The inverse association was robust when using MR Egger (OR: 0.29; 95% CI: 0.13, 0.63; P=0.003), weighted median (OR: 0.68; 95% CI: 0.57, 0.80; P<0.001), and weighted mode (OR: 0.64; 95% CI: 0.45, 0.92; P=0.019). Similarly, right handgrip strength was inversely related to GERD when exploiting IVW (OR: 0.70; 95% CI: 0.57, 0.85; P<0.001), MR Egger (OR: 0.34; 95% CI: 0.17, 0.70; P=0.004), and weighted median (OR: 0.75; 95% CI: 0.62, 0.89; P=0.001), though no relationship was found by weighted mode (OR: 0.88; 95% CI: 0.59, 1.30; P=0.518) (IDDF2023-ABS-0009 Figure 1. The potential causal association between handgrip strength and gastroesophageal reflux disease in European populations).

Conclusions Handgrip strength was inversely correlated with GERD. Further MR studies performed in other ethnicities are needed.

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Abstract IDDF2023-ABS-0009 Figure 1

The potential causal association between handgrip strength and gastroesophageal reflux disease in European populations