Background:Genetic factors that influence kidney traits have been understudied for low-frequency and ancestry-specific variants.Methods:This study used imputed whole-genome sequencing from the Trans-Omics for Precision Medicine project to identify novel loci for estimated glomerular filtration rate and urine albumin-to-creatinine ratio in up to 12 207 Hispanics/Latinos. Replication was performed in the Women’s Health Initiative and the UK Biobank when variants were available.Results:Two low-frequency intronic variants were associated with estimated glomerular filtration rate (rs58720902 at AQR, minor allele frequency=0.01, P=1.6×10⁻⁸) or urine albumin-to-creatinine ratio (rs527493184 at ZBTB16, minor allele frequency=0.002, P=1.1×10⁻⁸). An additional variant at PRNT (rs2422935, minor allele frequency=0.54, P=2.89×10⁻⁸) was significantly associated with estimated glomerular filtration rate in meta-analysis with replication samples. We also identified 2 known loci for urine albumin-to-creatinine ratio (BCL2L11 rs116907128, P=5.6×10⁻⁸ and HBB rs344, P=9.3×10⁻¹¹) and validated 8 loci for urine albumin-to-creatinine ratio previously identified in the UK Biobank.Conclusions:Our study shows gains in gene discovery when using dense imputation from multi-ethnic whole-genome sequencing data in admixed Hispanics/Latinos. It also highlights limitations in genetic research of kidney traits, including the lack of suitable replication samples for variants that are more common in non-European ancestry and those at low frequency in populations.

中文翻译：

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使用密集推算全基因组测序数据进行西班牙裔/拉丁裔肾脏特征的全基因组关联：西班牙裔社区健康研究/拉丁裔研究。


背景：影响肾脏性状的遗传因素已得到充分研究，以了解低频和血统特异性变异。方法：本研究使用精准医学跨组学项目的推算全基因组测序来识别估计肾小球滤过率和肾小球滤过率的新位点。多达 12 207 名西班牙裔/拉丁裔的尿白蛋白与肌酐比率。当变异可用时，在妇女健康倡议和英国生物库中进行复制。结果：两个低频内含子变异与估计的肾小球滤过率相关（ AQR的 rs58720902，次要等位基因频率 = 0.01， P = 1.6×10 ^-8 ）或尿白蛋白肌酐比（ ZBTB16的rs527493184，次要等位基因频率=0.002， P =1.1×10 ^-8 ）。 PRNT的另一个变异（rs2422935，次要等位基因频率=0.54， P =2.89×10 ^-8 ）与复制样本的荟萃分析中估计的肾小球滤过率显着相关。我们还鉴定了 2 个已知的尿白蛋白肌酐比位点（ BCL2L11 rs116907128， P = 5.6×10 ^-8和HBB rs344， P = 9.3×10 ^-11 ），并之前验证了 8 个尿白蛋白肌酐比位点结论：我们的研究表明，当使用西班牙裔/拉丁裔混合种族的多种族全基因组测序数据的密集插补时，基因发现方面取得了进展。它还强调了肾脏性状遗传研究的局限性，包括缺乏适合非欧洲血统中更常见的变异和人群中频率较低的变异的复制样本。