title: Validated SNPs for eGFR and their associations with albuminuria.
abstract: 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.
authors.affiliation: NHLBI’s Framingham Heart Study and the Center for Population Studies, Framingham, MA 01702, USA.
authors.forename: Jaclyn W
authors.initials: JW
authors.lastname: Ellis
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Chen
authors.forename: Meredith C
authors.initials: MC
authors.lastname: Foster
authors.forename: Ching-Ti
authors.initials: CT
authors.lastname: Liu
authors.forename: Martin G
authors.initials: MG
authors.lastname: Larson
authors.forename: Ian
authors.initials: I
authors.lastname: de Boer
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.forename: Afshin
authors.initials: A
authors.lastname: Parsa
authors.forename: Murielle
authors.initials: M
authors.lastname: Bochud
authors.forename: Carsten A
authors.initials: CA
authors.lastname: Böger
authors.forename: Linda
authors.initials: L
authors.lastname: Kao
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Conall M
authors.initials: CM
authors.lastname: O'Seaghdha
mesh_terms: D000328:Adult; D000368:Aged; D000418:Albumins / Q000032:analysis; D000419:Albuminuria / Q000235:genetics* / Q000503:physiopathology* / Q000652:urine; D044383:Black People / Q000235:genetics; D015331:Cohort Studies; D003404:Creatinine / Q000652:urine; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D044465:White People / Q000235:genetics
chemical_list: D000418:Albumins; D003404:Creatinine