Ethnic-specific associations between body mass index and gastric cancer: a Mendelian randomization study in European and Korean populations

Abstract

Background: Given the uncertainties surrounding the associations in previous epidemiological studies, we conducted linear and nonlinear Mendelian randomization (MR) studies to evaluate whether body mass index (BMI) associated with gastric cancer (GC) risk in European and Korean.

Methods: Genome-wide association study-summary statistics were used from the Pan-UK Biobank, the Genetic Investigation of Anthropometric Traits consortium, the K-CHIP consortium, and BioBank Japan. BMI-associated single nucleotide polymorphisms (SNPs) were used as instrumental variables (IVs) in MR to identify the association between BMI and GC. Both linear and nonlinear MR analyses were performed. Sensitivity analyses were also conducted for individuals below or above a BMI of 24 kg/m².

Results: The study used 22 and 55 SNPs as IVs for BMI in European and Korean populations, respectively. Genetically predicted BMI was positively associated with GC risk in the European population (Odds ratio per 1 kg/m² increase; 95% CI = 1.17; 1.01-1.36 using simple median method), but no significant association was observed in the Korean population. However, the nonlinear MR identified a U-shaped association between BMI and GC in the Korean population, with both low and high BMIs associated with increased GC risk. A BMI of 24 kg/m² presented the lowest risk. Sensitivity analyses did not yield any genome-wide significant SNPs.

Conclusion: While MR analysis suggests a linear association between BMI and GC in those of European ancestry, nonlinear MR hints at a U-shaped association in Koreans. This suggests the association between BMI and GC risk may vary according to ethnic ancestry.

Keywords: Body mass index; Instrument variable; Nonlinear Mendelian randomization; Stomach neoplasms.