Validated SNPs for eGFR and their associations with albuminuria
Validated SNPs for eGFR and their associations with albuminuria
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DOI：
10.1093/hmg/dds138
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发表时间：
2012-07-15
影响因子：
3.5
通讯作者：
O'Seaghdha, Conall M.
中科院分区：
文献类型：
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作者：
Ellis, Jaclyn W.;Chen, Ming-Huei;O'Seaghdha, Conall M.
蛋白尿和肾小球滤过率降低是慢性肾脏病(CKD)的表现，预示终末期肾脏疾病、急性肾损伤、心血管疾病和死亡。我们假设，与估计的肾小球滤过率(EGFR)相关的SNPs也与蛋白尿有关。在CKDGen Consortium队列中(31 580人，欧洲血统)，我们测试了16个与EGFR相关的SNPs与尿白蛋白/肌酐比(UACR)和蛋白尿[UACR 25 mg/g(女性)；17 mg/g(男性)]的相关性。与此同时，在CARE肾脏联盟(n 5569，非洲血统)中，我们测试了7个与EGFR相关的SNP与UACR的关联。我们在CKDGEN和CARE中分别使用了0.003(0.05/16)和0.007(0.05/7)的Bonferroni校正P值。我们还使用贝塔加权的基因分值评估了16个EGFR SNPs是否与UACR相关。在CKDGen联合体中，SHROOM3基因中rs17319721的小A等位基因与较低的EGFR相关，与较低的ln(UACR)水平相关(β0.034，P值0.0002)。没有其他与EGFR相关的SNPs达到Bonferroni校正的UACR或蛋白尿的P值阈值0.003。在CARE肾脏联盟中，SNPs和UACR之间没有关联，P值为0.007。虽然我们发现基因分值与蛋白尿有关(P 0.0006)，但这一结果几乎完全是由已知的SHROOM3变异rs17319721驱动的。去除rs17319721导致P值为0.03，表明残留聚集信号较弱。没有之前被证明与较低的EGFR相关的等位基因与UACR或蛋白尿相关，这表明这些特征可能有不同的遗传成分。
Albuminuria and reduced glomerular filtration rate are manifestations of chronic kidney disease (CKD) that predict end-stage renal disease, acute kidney injury, cardiovascular disease and death. We hypothesized that SNPs identified in association with the estimated glomerular filtration rate (eGFR) would also be associated with albuminuria. Within the CKDGen Consortium cohort (n 31 580, European ancestry), we tested 16 eGFR-associated SNPs for association with the urinary albumin-to-creatinine ratio (UACR) and albuminuria [UACR 25 mg/g (women); 17 mg/g (men)]. In parallel, within the CARe Renal Consortium (n 5569, African ancestry), we tested seven eGFR-associated SNPs for association with the UACR. We used a Bonferroni-corrected P-value of 0.003 (0.05/16) in CKDGen and 0.007 (0.05/7) in CARe. We also assessed whether the 16 eGFR SNPs were associated with the UACR in aggregate using a beta-weighted genotype score. In the CKDGen Consortium, the minor A allele of rs17319721 in the SHROOM3 gene, known to be associated with a lower eGFR, was associated with lower ln(UACR) levels (beta 0.034, P-value 0.0002). No additional eGFR-associated SNPs met the Bonferroni-corrected P-value threshold of 0.003 for either UACR or albuminuria. In the CARe Renal Consortium, there were no associations between SNPs and UACR with a P 0.007. Although we found the genotype score to be associated with albuminuria (P 0.0006), this result was driven almost entirely by the known SHROOM3 variant, rs17319721. Removal of rs17319721 resulted in a P-value 0.03, indicating a weak residual aggregate signal. No alleles, previously demonstrated to be associated with a lower eGFR, were associated with the UACR or albuminuria, suggesting that there may be distinct genetic components for these traits.