Lim Aylwin Ming Wee, Lim Evan Unit, Chen Pei-Lung, Fann Cathy Shen Jang
Taiwan International Graduate Program in Molecular Medicine, National Yang Ming Chiao Tung University and Academia Sinica, Taipei 112304, Taiwan.
Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan.
iScience. 2024 Apr 25;27(7):109815. doi: 10.1016/j.isci.2024.109815. eCollection 2024 Jul 19.
Metabolic syndrome (MetS) is a collection of cardiovascular risk factors; however, the high prevalence and heterogeneity impede effective clinical management. We conducted unsupervised clustering on individuals from UK Biobank to reveal endotypes. Five MetS subgroups were identified: Cluster 1 (C1): non-descriptive, Cluster 2 (C2): hypertensive, Cluster 3 (C3): obese, Cluster 4 (C4): lipodystrophy-like, and Cluster 5 (C5): hyperglycemic. For all of the endotypes, we identified the corresponding cardiometabolic traits and their associations with clinical outcomes. Genome-wide association studies (GWASs) were conducted to identify associated genotypic traits. We then determined endotype-specific genotypic traits and constructed polygenic risk score (PRS) models specific to each endotype. GWAS of each MetS clusters revealed different genotypic traits. C1 GWAS revealed novel findings of , , , and . Intriguingly, C1, C3, and C4 were associated with genes highly expressed in brain tissues. MetS clusters with comparable phenotypic and genotypic traits were identified in Taiwan Biobank.
代谢综合征（MetS）是一组心血管危险因素；然而，其高患病率和异质性阻碍了有效的临床管理。我们对英国生物银行的个体进行了无监督聚类以揭示内型。确定了五个MetS亚组：聚类1（C1）：无特定描述型，聚类2（C2）：高血压型，聚类3（C3）：肥胖型，聚类4（C4）：脂肪营养不良样型，以及聚类5（C5）：高血糖型。对于所有内型，我们确定了相应的心脏代谢特征及其与临床结局的关联。进行了全基因组关联研究（GWAS）以确定相关的基因型特征。然后我们确定了内型特异性基因型特征，并构建了针对每种内型的多基因风险评分（PRS）模型。每个MetS聚类的GWAS揭示了不同的基因型特征。C1的GWAS揭示了……、……、……和……的新发现。有趣的是，C1、C3和C4与在脑组织中高表达的基因相关。在台湾生物银行中鉴定出了具有可比表型和基因型特征的MetS聚类。 （注：原文中C1的GWAS部分有缺失内容未完整翻译）
