鉴于先前流行病学研究中相关性的不确定性，我们进行了线性和非线性孟德尔随机化（MR）研究，以评估体重指数（BMI）是否与欧洲和韩国的胃癌（GC）风险相关。全基因组关联研究-汇总统计数据来自泛英国生物银行、人体测量性状基因调查联盟、K-CHIP 联盟和日本生物银行。 BMI 相关的单核苷酸多态性 (SNP) 被用作 MR 中的工具变量 (IV)，以识别 BMI 和 GC 之间的关联。进行了线性和非线性 MR 分析。还对 BMI 低于或高于 24 kg/m2 的个体进行了敏感性分析。该研究分别使用 22 个和 55 个 SNP 作为欧洲和韩国人群 BMI 的 IV。在欧洲人群中，基因预测的 BMI 与 GC 风险呈正相关（每增加 1 kg/m2 的优势比；95% CI = 1.17；使用简单中位数法为 1.01-1.36），但在韩国人群中未观察到显着关联。然而，非线性 MR 发现韩国人群中 BMI 和 GC 之间存在 U 形关联，低和高 BMI 都与 GC 风险增加相关。 BMI 为 24 kg/m2 的风险最低。敏感性分析没有产生任何全基因组显着的 SNP。虽然 MR 分析表明欧洲血统的 BMI 和 GC 之间存在线性关联，但非线性 MR 暗示韩国人的 BMI 和 GC 之间存在 U 形关联。这表明 BMI 和 GC 风险之间的关联可能会因种族血统而异。© 2023。作者获得国际胃癌协会和日本胃癌协会的独家许可。

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.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.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.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.© 2023. The Author(s) under exclusive licence to The International Gastric Cancer Association and The Japanese Gastric Cancer Association.