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GWAS 研究结果提高了血脂谱特征的基因组预测准确性:德黑兰心脏代谢遗传研究。

GWAS findings improved genomic prediction accuracy of lipid profile traits: Tehran Cardiometabolic Genetic Study.

机构信息

Cellular and Molecular Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, POBox: 19195-4763, Tehran, Iran.

Department of Animal Science, Safiabad-Dezful Agricultural and Natural Resources Research and Education Center, Agricultural Research, Education & Extension Organization (AREEO), Dezful, Iran.

出版信息

Sci Rep. 2021 Mar 11;11(1):5780. doi: 10.1038/s41598-021-85203-8.

Abstract

In recent decades, ongoing GWAS findings discovered novel therapeutic modifications such as whole-genome risk prediction in particular. Here, we proposed a method based on integrating the traditional genomic best linear unbiased prediction (gBLUP) approach with GWAS information to boost genetic prediction accuracy and gene-based heritability estimation. This study was conducted in the framework of the Tehran Cardio-metabolic Genetic study (TCGS) containing 14,827 individuals and 649,932 SNP markers. Five SNP subsets were selected based on GWAS results: top 1%, 5%, 10%, 50% significant SNPs, and reported associated SNPs in previous studies. Furthermore, we randomly selected subsets as large as every five subsets. Prediction accuracy has been investigated on lipid profile traits with a tenfold and 10-repeat cross-validation algorithm by the gBLUP method. Our results revealed that genetic prediction based on selected subsets of SNPs obtained from the dataset outperformed the subsets from previously reported SNPs. Selected SNPs' subsets acquired a more precise prediction than whole SNPs and much higher than randomly selected SNPs. Also, common SNPs with the most captured prediction accuracy in the selected sets caught the highest gene-based heritability. However, it is better to be mindful of the fact that a small number of SNPs obtained from GWAS results could capture a highly notable proportion of variance and prediction accuracy.

摘要

近几十年来,不断进行的全基因组关联研究(GWAS)发现了新的治疗方法,如全基因组风险预测等。在这里,我们提出了一种方法,该方法基于整合传统的基因组最佳线性无偏预测(gBLUP)方法和 GWAS 信息,以提高遗传预测准确性和基于基因的遗传力估计。本研究在包含 14827 个人和 649932 个 SNP 标记的德黑兰心血管代谢遗传研究(TCGS)框架内进行。根据 GWAS 结果选择了五个 SNP 子集:前 1%、5%、10%、50%显著 SNP 和以前研究中报道的相关 SNP。此外,我们还随机选择了与每个五个子集一样大的子集。使用 gBLUP 方法,通过十倍交叉验证算法和 10 次重复交叉验证算法,对血脂特征进行了预测准确性研究。我们的结果表明,基于从数据集中选择的 SNP 子集进行遗传预测的效果优于从以前报道的 SNP 中选择的子集。选择的 SNP 子集的预测比全 SNP 更准确,比随机选择的 SNP 高得多。此外,在选定的 SNP 集中,具有最高捕获预测准确性的常见 SNP 捕获了最高的基于基因的遗传力。然而,我们需要注意的是,从 GWAS 结果中获得的少数 SNP 可以捕获高度显著的方差和预测准确性。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e24f/7952573/b9353fb89aa5/41598_2021_85203_Fig1_HTML.jpg

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