{"title":"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。","authors":"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","doi":"10.1002/oby.24335","DOIUrl":null,"url":null,"abstract":"<div>\n \n \n <section>\n \n <h3> Objective</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Methods</h3>\n \n <p>We conducted genome-wide association studies of BMI (<i>n</i> = 95,488) and body fat percentage (BFP; <i>n</i> = 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.</p>\n </section>\n \n <section>\n \n <h3> Results</h3>\n \n <p>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.</p>\n </section>\n \n <section>\n \n <h3> Conclusions</h3>\n \n <p>These findings reveal novel adiposity loci and underscore the clinical utility of adiposity-related genetics for personalized health.</p>\n </section>\n </div>","PeriodicalId":215,"journal":{"name":"Obesity","volume":"33 9","pages":"1765-1778"},"PeriodicalIF":4.7000,"publicationDate":"2025-08-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Unraveling the genetic link: causal effects and PRS predictions of adiposity-related health conditions in East Asian individuals\",\"authors\":\"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\",\"doi\":\"10.1002/oby.24335\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<div>\\n \\n \\n <section>\\n \\n <h3> Objective</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Methods</h3>\\n \\n <p>We conducted genome-wide association studies of BMI (<i>n</i> = 95,488) and body fat percentage (BFP; <i>n</i> = 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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Results</h3>\\n \\n <p>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.</p>\\n </section>\\n \\n <section>\\n \\n <h3> Conclusions</h3>\\n \\n <p>These findings reveal novel adiposity loci and underscore the clinical utility of adiposity-related genetics for personalized health.</p>\\n </section>\\n </div>\",\"PeriodicalId\":215,\"journal\":{\"name\":\"Obesity\",\"volume\":\"33 9\",\"pages\":\"1765-1778\"},\"PeriodicalIF\":4.7000,\"publicationDate\":\"2025-08-14\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Obesity\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://onlinelibrary.wiley.com/doi/10.1002/oby.24335\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"ENDOCRINOLOGY & METABOLISM\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Obesity","FirstCategoryId":"3","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/oby.24335","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"ENDOCRINOLOGY & METABOLISM","Score":null,"Total":0}
Unraveling the genetic link: causal effects and PRS predictions of adiposity-related health conditions in East Asian individuals
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.
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.
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