小柯机器人

澳大利亚昆士兰大学Loic Yengo及其团队的最新研究通过使用多基因评分，改进了同种和跨物种全基因组关联研究（GWASs）的能力。相关论文于2023年9月18日发表在《自然-遗传学》杂志上。

研究人员通过理论、模拟和对真实数据的应用表明，调整GWAS分析的多基因评分（PGS）增加了所有人种的统计能力。研究应用这种方法分析了三个大型生物库中的七个特征，参与者包含东亚人（总共n=340,000），并发现了139个其他的跨性状关联。研究人员还提出了一个两阶段的荟萃分析策略，其中，在主队列中，使用第一轮标准荟萃分析的PGS重新运行PGS调整后的GWAS。

平均而言，对性状来说这种方法使检测到的关联数量增加了1.26倍（范围增加了1.07到1.76倍）。总之，该研究表明在代表性不足的人群中使用PGSs增加了GWAS的能力，并有利于这种分析方法在未来GWAS荟萃分析中的应用。

据介绍，全基因组关联研究主要在欧洲血统的人群中进行，这限制了其发现向其他人群的转移。

附：英文原文

Title: Boosting the power of genome-wide association studies within and across ancestries by using polygenic scores

Author: Campos, Adrian I., Namba, Shinichi, Lin, Shu-Chin, Nam, Kisung, Sidorenko, Julia, Wang, Huanwei, Kamatani, Yoichiro, Wang, Ling-Hua, Lee, Seunggeun, Lin, Yen-Feng, Feng, Yen-Chen Anne, Okada, Yukinori, Visscher, Peter M., Yengo, Loic

Issue&Volume: 2023-09-18

Abstract: Genome-wide association studies (GWASs) have been mostly conducted in populations of European ancestry, which currently limits the transferability of their findings to other populations. Here, we show, through theory, simulations and applications to real data, that adjustment of GWAS analyses for polygenic scores (PGSs) increases the statistical power for discovery across all ancestries. We applied this method to analyze seven traits available in three large biobanks with participants of East Asian ancestry (n=340,000 in total) and report 139 additional associations across traits. We also present a two-stage meta-analysis strategy whereby, in contributing cohorts, a PGS-adjusted GWAS is rerun using PGSs derived from a first round of a standard meta-analysis. On average, across traits, this approach yields a 1.26-fold increase in the number of detected associations (range 1.07- to 1.76-fold increase). Altogether, our study demonstrates the value of using PGSs to increase the power of GWASs in underrepresented populations and promotes such an analytical strategy for future GWAS meta-analyses.

DOI: 10.1038/s41588-023-01500-0

Source: https://www.nature.com/articles/s41588-023-01500-0

Nature Genetics：《自然—遗传学》，创刊于1992年。隶属于施普林格·自然出版集团，最新IF：41.307
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