Bioinformatics Core, Weill Cornell Medicine-Qatar, Education City, Doha, Qatar.
College of Health and Life Sciences, Hamad Bin Khalifa University, Education City, Doha, Qatar.
Nat Commun. 2021 Feb 23;12(1):1250. doi: 10.1038/s41467-021-21381-3.
Clinical laboratory tests play a pivotal role in medical decision making, but little is known about their genetic variability between populations. We report a genome-wide association study with 45 clinically relevant traits from the population of Qatar using a whole genome sequencing approach in a discovery set of 6218 individuals and replication in 7768 subjects. Trait heritability is more similar between Qatari and European populations (r = 0.81) than with Africans (r = 0.44). We identify 281 distinct variant-trait-associations at genome wide significance that replicate known associations. Allele frequencies for replicated loci show higher correlations with European (r = 0.94) than with African (r = 0.85) or Japanese (r = 0.80) populations. We find differences in linkage disequilibrium patterns and in effect sizes of the replicated loci compared to previous reports. We also report 17 novel and Qatari-predominate signals providing insights into the biological pathways regulating these traits. We observe that European-derived polygenic scores (PGS) have reduced predictive performance in the Qatari population which could have implications for the translation of PGS between populations and their future application in precision medicine.
临床实验室检测在医学决策中起着关键作用，但人们对其在不同人群中的遗传变异性知之甚少。我们使用全基因组测序方法，在一个由 6218 个人组成的发现集中，对来自卡塔尔的 45 种具有临床相关性的特征进行了全基因组关联研究，并在 7768 名受试者中进行了复制。卡塔尔人和欧洲人之间的特征遗传力更为相似（r=0.81），而与非洲人（r=0.44）相比则不那么相似。我们确定了 281 个独特的变体-特征关联，达到了全基因组显著性水平，并复制了已知的关联。在复制的基因座中，等位基因频率与欧洲人（r=0.94）的相关性高于非洲人（r=0.85）或日本人（r=0.80）。与之前的报告相比，我们发现复制的基因座的连锁不平衡模式和效应大小存在差异。我们还报告了 17 个新的、以卡塔尔为主的信号，为调节这些特征的生物学途径提供了深入了解。我们观察到，欧洲衍生的多基因评分（PGS）在卡塔尔人群中的预测性能降低，这可能对 PGS 在不同人群之间的转化及其在精准医学中的未来应用产生影响。
