Unraveling the genetic link: causal effects and PRS predictions of adiposity-related health conditions in East Asian individuals

IF 4.7 2区医学 Q1 ENDOCRINOLOGY & METABOLISM

Obesity Pub Date : 2025-08-14 DOI:10.1002/oby.24335

Ying-Ju Lin, Ju-Pi Li, Ting-Yuan Liu, Jian-Shiun Chiou, Hsing-Fang Lu, Kuyuri Ariyoshi, Shunsuke Uchiyama, Chikashi Terao, Jai-Sing Yang, Chen-Hsing Chou, Wen-Miin Liang, I-Ching Chou, Cheng-Wen Lin, Ting-Hsu Lin, Chiu-Chu Liao, Shao-Mei Huang, Fuu-Jen Tsai

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引用次数: 0

Abstract

Objective

Although associations of adiposity with metabolic, cardiovascular, and liver diseases are known, the genetic links, causal effects, and polygenic risk score (PRS) predictions for these health conditions in East Asian individuals remain unclear.

Methods

We conducted genome-wide association studies of BMI (n = 95,488) and body fat percentage (BFP; n = 83,448) in Taiwanese individuals from Taiwan Biobank data, followed by cross-trait genetic correlation and bidirectional Mendelian randomization in four East Asian biobanks. BMI and BFP PRS were constructed and validated in the China Medical University Hospital and Biobank Japan databases.

Results

We identified 41 BMI and 22 BFP loci, including novel loci. Genetically predicted higher adiposity correlated with increased risk of metabolic syndrome, cardiovascular disease, hypertension, and elevated liver enzymes. Bidirectional Mendelian randomization revealed a causal effect of adiposity on glycosylated hemoglobin, systolic blood pressure, liver enzymes, and cholelithiasis, with no reverse causality. After adjusting for type 2 diabetes, the effect on glycemic traits diminished, suggesting a strong influence of diabetes-related loci. BMI and BFP PRS robustly predicted higher risk and earlier onset of type 2 diabetes, hypertension, cholelithiasis, and liver dysfunction in East Asian individuals.

Conclusions

These findings reveal novel adiposity loci and underscore the clinical utility of adiposity-related genetics for personalized health.

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揭示遗传联系：东亚个体肥胖相关健康状况的因果效应和PRS预测。

目的：虽然肥胖与代谢、心血管和肝脏疾病的关联是已知的，但东亚个体这些健康状况的遗传联系、因果效应和多基因风险评分（PRS）预测仍不清楚。方法：我们进行了BMI （n = 95,488）和体脂率(BFP；n = 83,448)，然后在四个东亚生物库中进行交叉性状遗传相关和双向孟德尔随机化。在中国医科大学附属医院和日本Biobank数据库中构建BMI和BFP PRS并进行验证。结果：我们确定了41个BMI位点和22个BFP位点，包括新的位点。遗传预测较高的肥胖与代谢综合征、心血管疾病、高血压和肝酶升高的风险增加相关。双向孟德尔随机化结果显示，肥胖对糖化血红蛋白、收缩压、肝酶和胆石症有因果关系，无反向因果关系。在对2型糖尿病进行调整后，对血糖特征的影响减弱，这表明糖尿病相关基因的影响很大。BMI和BFP PRS有力地预测了东亚人群中2型糖尿病、高血压、胆石症和肝功能障碍的高风险和早期发病。结论：这些发现揭示了新的肥胖基因座，并强调了肥胖相关遗传学在个性化健康方面的临床应用。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Obesity 医学-内分泌学与代谢

CiteScore

11.70

自引率

1.40%

发文量

261

审稿时长

2-4 weeks

期刊介绍： Obesity is the official journal of The Obesity Society and is the premier source of information for increasing knowledge, fostering translational research from basic to population science, and promoting better treatment for people with obesity. Obesity publishes important peer-reviewed research and cutting-edge reviews, commentaries, and public health and medical developments.