Journal of Epidemiology
Online ISSN : 1349-9092
Print ISSN : 0917-5040
ISSN-L : 0917-5040


BMI and Cardiometabolic Traits in Japanese: A Mendelian Randomization Study
Mako NagayoshiAsahi HishidaTomonori ShimizuYasufumi KatoYoko KuboRieko OkadaTakashi TamuraJun OtonariHiroaki IkezakiMegumi HaraYuichiro NishidaIsao OzeYuriko N. KoyanagiYohko NakamuraMiho KusakabeRie IbusukiKeiichi ShibuyaSadao SuzukiTakeshi NishiyamaTeruhide KoyamaEtsuko OzakiKiyonori KurikiNaoyuki TakashimaYasuyuki NakamuraSakurako Katsuura-KamanoKokichi ArisawaMasahiro NakatochiYukihide MomozawaKenji TakeuchiKenji Wakai
ジャーナル オープンアクセス 早期公開

論文ID: JE20220154

2版: 2023/05/31
1版: 2023/01/28

Background: Although many observational studies have demonstrated significant relationships between obesity and cardiometabolic traits, the causality of these relationships in East Asians remains to be elucidated.

Methods: We conducted individual-level Mendelian randomization (MR) analyses targeting 14,083 participants in the Japan Multi-Institutional Collaborative Cohort Study and two-sample MR analyses using summary statistics based on genome-wide association study data from 173,430 Japanese. Using 83 body mass index (BMI)-related loci, genetic risk scores (GRS) for BMI were calculated, and the effects of BMI on cardiometabolic traits were examined for individual-level MR analyses using the two-stage least squares estimator method. The β-coefficients and standard errors for the per-allele association of each single-nucleotide polymorphism as well as all outcomes, or odds ratios with 95% confidence intervals were calculated in the two-sample MR analyses.

Results: In individual-level MR analyses, the GRS of BMI was not significantly associated with any cardiometabolic traits. In two-sample MR analyses, higher BMI was associated with increased risks of higher blood pressure, triglycerides, and uric acid, as well as lower high-density-lipoprotein cholesterol and eGFR. The associations of BMI with type 2 diabetes in two-sample MR analyses were inconsistent using different methods, including the directions.

Conclusion: The results of this study suggest that, even among the Japanese, an East Asian population with low levels of obesity, higher BMI could be causally associated with the development of a variety of cardiometabolic traits. Causality in those associations should be clarified in future studies with larger populations, especially those of BMI with type 2 diabetes.

© 2023 Mako Nagayoshi et al.

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