Estimating heritability explained by local ancestry and evaluating stratification bias in admixture mapping from summary statistics.
Estimating heritability explained by local ancestry and evaluating stratification bias in admixture mapping from summary statistics.
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估计由当地血统解释的遗传力，并根据汇总统计评估混合映射中的分层偏差。
DOI：
10.1101/2023.04.10.536252
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发表时间：
2023
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作者：
Chan,TszFung;Rui,Xinyue;Conti,DavidV;Fornage,Myriam;Graff,Mariaelisa;Haessler,Jeffrey;Haiman,Christopher;Highland,HeatherM;Jung,SuYon;Kenny,Eimear;Kooperberg,Charles;Marchland,LoicLe;North,KariE;Tao,Ran;Wojcik,Genevieve;
在混合群体中，由本地祖先标记解释的遗传力为了解复杂疾病或性状的遗传结构提供了重要的见解。由于祖先群体的人口结构，估计可能容易受到偏差的影响。在这里，我们提出了混合映射汇总统计（HAMSTA）的遗传力估计，这是一种利用混合映射汇总统计来推断由当地祖先解释的遗传力的方法，同时调整了由于祖先分层造成的偏差。通过广泛的模拟，我们证明hamsta估计值与现有方法相比是近似无偏的，并且对祖先分层具有鲁棒性。在存在祖先分层的情况下，我们展示了hamsta衍生的采样方案，与现有的FWER估计方法不同，为混合物映射提供了校准的家庭误差率（FWER）约5%。我们使用基因组学和流行病学（PAGE）研究将HAMSTA应用于人口结构中多达15,988名自我报告的非裔美国人个体的20个定量表型。我们观察到20种表型的h - γ2范围为0.0025至0.033（平均h - γ2 = 0.012±9.2 × 10−4），换算成h - 2范围为0.062至0.85（平均h - 2 = 0.30±0.023）。在这些表型中，我们发现在目前的混合作图研究中，很少有证据表明由于祖先群体分层造成的膨胀（平均膨胀因子为0.99±0.001）。总体而言，HAMSTA提供了一种快速而强大的方法来估计全基因组遗传力和评估混合作图研究的测试统计偏差。
The heritability explained by local ancestry markers in an admixed population () provides crucial insight into the genetic architecture of a complex disease or trait. Estimation ofcan be susceptible to biases due to population structure in ancestral populations. Here, we present heritability estimation from admixture mapping summary statistics (HAMSTA), an approach that uses summary statistics from admixture mapping to infer heritability explained by local ancestry while adjusting for biases due to ancestral stratification. Through extensive simulations, we demonstrate that HAMSTAestimates are approximately unbiased and are robust to ancestral stratification compared to existing approaches. In the presence of ancestral stratification, we show a HAMSTA-derived sampling scheme provides a calibrated family-wise error rate (FWER) of ∼5% for admixture mapping, unlike existing FWER estimation approaches. We apply HAMSTA to 20 quantitative phenotypes of up to 15,988 self-reported African American individuals in the Population Architecture using Genomics and Epidemiology (PAGE) study. We observe hˆγ2 in the 20 phenotypes range from 0.0025 to 0.033 (mean hˆγ2 = 0.012 ± 9.2 × 10−4), which translates to hˆ2 ranging from 0.062 to 0.85 (mean hˆ2 = 0.30 ± 0.023). Across these phenotypes we find little evidence of inflation due to ancestral population stratification in current admixture mapping studies (mean inflation factor of 0.99 ± 0.001). Overall, HAMSTA provides a fast and powerful approach to estimate genome-wide heritability and evaluate biases in test statistics of admixture mapping studies.