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希腊队列中身高多基因风险评分的开发与验证:与血压测量值的关联

Development and validation of a polygenic risk score for height in a Greek cohort: Association with blood pressure measurements.

作者信息

Kalafati Ioanna Panagiota, Tsifintaris Margaritis, Dimitriou Maria, Grigoriou Effimia, Moulos Panagiotis, Dedoussis George V

机构信息

Department of Nutrition and Dietetics, School of Physical Education, Sport Science and Dietetics, University of Thessaly, Trikala, Greece.

Department of Nutrition and Dietetics, School of Health Science and Education, Harokopio University, Athens, Greece.

出版信息

Front Genet. 2025 May 1;16:1538975. doi: 10.3389/fgene.2025.1538975. eCollection 2025.

Abstract

Human height is a highly heritable trait. Genome-wide association studies have identified thousands of genetic variants linked to height, some of which exhibit pleiotropic effects. However, population-specific genome-wide Polygenic Risk Scores (PRSs) for height for specific populations remain limited. In this study, we developed a PRS for height tailored to Greek individuals using a dataset of 1970 adults. We applied a robust, iterative PRS construction pipeline based on previously published methods to capture the unique genetic architecture of height in this population. Our analysis identified multiple significant heightassociated SNPs specific to the Greek population and the constructed Greek-specific PRS accounted for 10.8% of height variability. A significant overlap of height-associated SNPs with those of generalized PRSs from other European populations constitutes a positive marker for our methodology. Additionally, the PRS was associated with blood pressure, aligning with evidence from other studies. These results highlight the importance of applying a rigorous methodology in PRS derivation. This is the first genome-wide height-PRS for Greek adults, which may serve as a foundation for further studies on genetic risk prediction and personalized healthcare in underrepresented populations.

摘要

人类身高是一种高度可遗传的性状。全基因组关联研究已经确定了数千个与身高相关的基因变异,其中一些表现出多效性。然而,针对特定人群的全基因组身高多基因风险评分(PRSs)仍然有限。在本研究中,我们使用1970名成年人的数据集为希腊个体开发了一种量身定制的身高PRS。我们基于先前发表的方法应用了一个稳健的、迭代的PRS构建流程,以捕捉该人群中身高独特的遗传结构。我们的分析确定了多个希腊人群特有的与身高相关的显著单核苷酸多态性(SNPs),构建的希腊特异性PRS占身高变异性的10.8%。与其他欧洲人群的广义PRSs中与身高相关的SNPs有显著重叠,这是我们方法的一个积极标志。此外,该PRS与血压相关,这与其他研究的证据一致。这些结果突出了在PRS中应用严格方法的重要性。这是首个针对希腊成年人的全基因组身高PRS,可为在代表性不足人群中进一步开展遗传风险预测和个性化医疗研究奠定基础。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5a4/12108138/dfe8c6ebc949/fgene-16-1538975-g001.jpg

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