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Abstract：
UNASSIGNED: Genome-wide association studies (GWAS) have predominantly focused on populations of European and Asian ancestry, limiting our understanding of genetic factors influencing kidney disease in Sub-Saharan African (SSA) populations. This study presents the largest GWAS for urinary albumin-to-creatinine ratio (UACR) in SSA individuals, including 8,970 participants living in different African regions and an additional 9,705 non-resident individuals of African ancestry from the UK Biobank and African American cohorts.
UNASSIGNED: Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations.
UNASSIGNED: Two genome-wide significant (P < 5 × 10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained.
UNASSIGNED: This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes.
UNASSIGNED: Urine biomarkers and genotype data were obtained from two SSA cohorts (AWI-Gen and ARK), and two non-resident African-ancestry studies (UK Biobank and CKD-Gen Consortium). Association testing and meta-analyses were conducted, with subsequent fine-mapping, conditional analyses, and replication studies. Polygenic scores (PGS) were assessed for transferability across populations.
UNASSIGNED: Two genome-wide significant (P < 5 × 10-8) UACR-associated loci were identified, one in the BMP6 region on chromosome 6, in the meta-analysis of resident African individuals, and another in the HBB region on chromosome 11 in the meta-analysis of non-resident SSA individuals, as well as the combined meta-analysis of all studies. Replication of previous significant results confirmed associations in known UACR-associated regions, including THB53, GATM, and ARL15. PGS estimated using previous studies from European ancestry, African ancestry, and multi-ancestry cohorts exhibited limited transferability of PGS across populations, with less than 1% of observed variance explained.
UNASSIGNED: This study contributes novel insights into the genetic architecture of kidney disease in SSA populations, emphasizing the need for conducting genetic research in diverse cohorts. The identified loci provide a foundation for future investigations into the genetic susceptibility to chronic kidney disease in underrepresented African populations Additionally, there is a need to develop integrated scores using multi-omics data and risk factors specific to the African context to improve the accuracy of predicting disease outcomes.
摘要：
■全基因组关联研究（GWAS）主要集中在欧洲和亚洲血统的人群，限制了我们对影响撒哈拉以南非洲（SSA）人群肾脏疾病的遗传因素的理解。这项研究提出了最大的GWAS尿白蛋白肌酐比值（UACR）在SSA个体，包括居住在不同非洲地区的8,970名参与者，以及来自英国生物银行和非裔美国人队列的9,705名非洲血统的非居民个人。
■尿液生物标志物和基因型数据来自两个SSA队列（AWI-Gen和ARK），和两个非居民非洲血统研究（英国生物银行和CKD-Gen联盟）。进行了关联测试和荟萃分析，与随后的精细映射，条件分析，和复制研究。评估多基因评分（PGS）在人群中的可转移性。
■确定了两个全基因组显著（P<5×10-8）UACR相关基因座，一个在6号染色体上的BMP6区域，在非洲居民的荟萃分析中，在非居民SSA个体的荟萃分析中，另一个在11号染色体上的HBB区域，以及所有研究的综合荟萃分析。先前重要结果的复制证实了已知UACR相关区域的关联，包括THB53，GATM，ARL15PGS使用欧洲血统的先前研究估计，非洲血统,多血统队列在人群中表现出有限的PGS可转移性，用不到1%的观察到的方差解释。
■这项研究为SSA人群肾脏疾病的遗传结构提供了新的见解，强调需要在不同的队列中进行遗传研究。已确定的基因座为未来研究代表性不足的非洲人群中慢性肾脏疾病的遗传易感性奠定了基础。有必要使用多组学数据和特定于非洲背景的风险因素制定综合评分,以提高预测疾病结局的准确性.
■尿液生物标志物和基因型数据来自两个SSA队列（AWI-Gen和ARK），和两个非居民非洲血统研究（英国生物银行和CKD-Gen联盟）。进行了关联测试和荟萃分析，与随后的精细映射，条件分析，和复制研究。评估多基因评分（PGS）在人群中的可转移性。
■确定了两个全基因组显著（P<5×10-8）UACR相关基因座，一个在6号染色体上的BMP6区域，在非洲居民的荟萃分析中，在非居民SSA个体的荟萃分析中，另一个在11号染色体上的HBB区域，以及所有研究的综合荟萃分析。先前重要结果的复制证实了已知UACR相关区域的关联，包括THB53，GATM，ARL15PGS使用欧洲血统的先前研究估计，非洲血统,多血统队列在人群中表现出有限的PGS可转移性，用不到1%的观察到的方差解释。
■这项研究为SSA人群肾脏疾病的遗传结构提供了新的见解，强调需要在不同的队列中进行遗传研究。已确定的基因座为未来研究代表性不足的非洲人群中慢性肾脏疾病的遗传易感性奠定了基础。有必要使用多组学数据和特定于非洲背景的风险因素制定综合评分,以提高预测疾病结局的准确性.
