Australian Centre for Precision Health, University of South Australia, Adelaide, SA, 5000, Australia.
UniSA Allied Health and Human Performance, University of South Australia, Adelaide, SA, 5000, Australia.
Nat Commun. 2023 Feb 9;14(1):722. doi: 10.1038/s41467-023-36281-x.
Cross-ancestry genetic correlation is an important parameter to understand the genetic relationship between two ancestry groups. However, existing methods cannot properly account for ancestry-specific genetic architecture, which is diverse across ancestries, producing biased estimates of cross-ancestry genetic correlation. Here, we present a method to construct a genomic relationship matrix (GRM) that can correctly account for the relationship between ancestry-specific allele frequencies and ancestry-specific allelic effects. Through comprehensive simulations, we show that the proposed method outperforms existing methods in the estimations of SNP-based heritability and cross-ancestry genetic correlation. The proposed method is further applied to anthropometric and other complex traits from the UK Biobank data across ancestry groups. For obesity, the estimated genetic correlation between African and European ancestry cohorts is significantly different from unity, suggesting that obesity is genetically heterogenous between these two ancestries.
跨群体遗传相关是理解两个群体遗传关系的重要参数。然而，现有的方法不能很好地解释群体特异性遗传结构，这种结构在不同群体中是多种多样的，会导致跨群体遗传相关的估计产生偏差。在这里，我们提出了一种方法来构建一个可以正确解释群体特异性等位基因频率与群体特异性等位基因效应之间关系的基因组关系矩阵（GRM）。通过全面的模拟，我们表明，所提出的方法在 SNP 遗传力和跨群体遗传相关的估计中优于现有的方法。该方法进一步应用于 UK Biobank 数据中跨群体的人体测量和其他复杂特征。对于肥胖，非洲和欧洲血统队列之间的遗传相关性估计与单位值显著不同，这表明肥胖在这两个血统之间具有遗传异质性。
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