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Genome-Wide Admixture Mapping of Estimated Glomerular Filtration Rate and Chronic Kidney Disease Identifies European and African Ancestry-of-Origin Loci in Hispanic and Latino Individuals in the United States
Journal of the American Society of Nephrology ( IF 10.3 ) Pub Date : 2022-01-01 , DOI: 10.1681/asn.2021050617
Andrea R V R Horimoto 1 , Diane Xue 2 , Jianwen Cai 3 , James P Lash 4 , Martha L Daviglus 5 , Nora Franceschini 6 , Timothy A Thornton 1, 7
Affiliation  

Background

Admixture mapping is a powerful approach for gene mapping of complex traits that leverages the diverse genetic ancestry in populations with recent admixture, such as Hispanic or Latino individuals in the United States. These individuals have an increased risk of CKD.

Methods

We performed genome-wide admixture mapping for both CKD and eGFR in a sample of 12,601 participants from the Hispanic Community Health Study/Study of Latinos, with validation in a sample of 8191 Black participants from the Women’s Health Initiative (WHI). We also compared the findings with those from a conventional genome-wide association study.

Results

Three novel ancestry-of-origin loci were identified on chromosomes 2, 14, and 15 for CKD and eGFR. The chromosome 2 locus comprises two European ancestry regions encompassing the FSHR and NRXN1 genes, with European ancestry at this locus associated with increased CKD risk. The chromosome 14 locus, found within the DLK1-DIO3 imprinted domain, was associated with lower eGFR and driven by European ancestry. The eGFR-associated locus on chromosome 15 included intronic variants of RYR3 and was within an African-specific genomic region associated with higher eGFR. The genome-wide association study failed to identify significant associations in these regions. We validated the chromosome 14 and 15 loci associated with eGFR in the WHI Black participants.

Conclusions

This study provides evidence of shared ancestry-specific genomic regions influencing eGFR in Hispanic or Latino individuals and Black individuals and illustrates the potential for leveraging genetic ancestry in recently admixed populations for the discovery of novel candidate loci for kidney phenotypes.



中文翻译:


估计肾小球滤过率和慢性肾脏病的全基因组混合图谱确定了美国西班牙裔和拉丁裔个体的欧洲和非洲血统基因座


 背景


混合作图是一种对复杂性状进行基因作图的强大方法,它利用了最近混合的人群(例如美国的西班牙裔或拉丁裔个体)的不同遗传血统。这些人患 CKD 的风险增加。

 方法


我们对来自西班牙社区健康研究/拉丁裔研究的 12,601 名参与者样本进行了 CKD 和 eGFR 的全基因组混合图谱分析,并在来自妇女健康倡议 (WHI) 的 8191 名黑人参与者样本中进行了验证。我们还将这些结果与传统的全基因组关联研究的结果进行了比较。

 结果


在 2、14 和 15 号染色体上鉴定出 3 个新的 CKD 和 eGFR 起源基因座。 2 号染色体基因座包含两个包含FSHRNRXN1基因的欧洲血统区域,该基因座的欧洲血统与 CKD 风险增加相关。在DLK1-DIO3印迹域内发现的 14 号染色体位点与较低的 eGFR 相关,并由欧洲血统驱动。 15 号染色体上的 eGFR 相关位点包括RYR3的内含子变体,并且位于与较高 eGFR 相关的非洲特异性基因组区域内。全基因组关联研究未能确定这些区域的显着关联。我们验证了 WHI 黑人参与者中与 eGFR 相关的 14 号和 15 号染色体位点。

 结论


这项研究提供了影响西班牙裔或拉丁裔个体和黑人个体的 eGFR 的共同祖先特定基因组区域的证据,并说明了利用最近混合人群中的遗传祖先来发现肾脏表型的新候选基因座的潜力。

更新日期:2021-12-31
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