Rare mutations associating with serum creatinine and chronic kidney disease.
Cast your vote
You can rate an item by clicking the amount of stars they wish to award to this item.
When enough users have cast their vote on this item, the average rating will also be shown.
Your vote was cast
Thank you for your feedback
Thank you for your feedback
Indridason, Olafur S
Eyjolfsson, Gudmundur Ingi
Magnusson, Olafur Th
Gudbjartsson, Daniel F
MetadataShow full item record
CitationHum. Mol. Genet. 2014, 23 (25):6935-43
AbstractChronic kidney disease (CKD) is a complex disorder with a strong genetic component. A number of common sequence variants have been found to associate with serum creatinine (SCr), estimated glomerular filtration rate (eGFR) and/or CKD. We imputed 24 million single-nucleotide polymorphisms and insertions/deletions identified by whole-genome sequencing of 2230 Icelanders into 81 656 chip-typed individuals and 112 630 relatives of genotyped individuals over the age of 18 with SCr measurements. The large set of sequenced individuals allowed accurate imputation of variants to a minor allele frequency (MAF) of 0.1%. We tested the imputed variants for association with SCr. In addition to replicating established loci, we discovered missense and loss-of-function variants associating with SCr in three solute carriers (SLC6A19, SLC25A45 and SLC47A1) and two E3 ubiquitin ligases (RNF186 and RNF128). All the variants are within coding sequences and all but one are rare (MAF <2%) with SCr effects between 0.085 and 0.129 standard deviations. These rare variants have a larger effect on SCr than previously reported common variants, explaining 0.5% of the variability of SCr in Icelanders in addition to the 1% already accounted for. We tested the five variants associating with SCr for association with CKD in an Icelandic sample of 15 594 cases and 291 428 controls. Three of the variants also associated with CKD. These variants may either affect kidney function or creatinine synthesis and excretion. Of note were four mutations in SLC6A19 that associate with reduced SCr, three of which have been shown to cause Hartnup disease.
DescriptionTo access publisher's full text version of this article click on the hyperlink at the bottom of the page
RightsArchived with thanks to Human molecular genetics
- Genome-Wide Association Study of Renal Function Traits: Results from the Japan Multi-Institutional Collaborative Cohort Study.
- Authors: Hishida A, Nakatochi M, Akiyama M, Kamatani Y, Nishiyama T, Ito H, Oze I, Nishida Y, Hara M, Takashima N, Turin TC, Watanabe M, Suzuki S, Ibusuki R, Shimoshikiryo I, Nakamura Y, Mikami H, Ikezaki H, Furusyo N, Kuriki K, Endoh K, Koyama T, Matsui D, Uemura H, Arisawa K, Sasakabe T, Okada R, Kawai S, Naito M, Momozawa Y, Kubo M, Wakai K, Japan Multi-Institutional Collaborative Cohort (J-MICC) Study Group.
- Issue date: 2018
- Genetic loci associated with renal function measures and chronic kidney disease in children: the Pediatric Investigation for Genetic Factors Linked with Renal Progression Consortium.
- Authors: Wuttke M, Wong CS, Wühl E, Epting D, Luo L, Hoppmann A, Doyon A, Li Y, CKDGen Consortium., Sözeri B, Thurn D, Helmstädter M, Huber TB, Blydt-Hansen TD, Kramer-Zucker A, Mehls O, Melk A, Querfeld U, Furth SL, Warady BA, Schaefer F, Köttgen A
- Issue date: 2016 Feb
- Association of variants at UMOD with chronic kidney disease and kidney stones-role of age and comorbid diseases.
- Authors: Gudbjartsson DF, Holm H, Indridason OS, Thorleifsson G, Edvardsson V, Sulem P, de Vegt F, d'Ancona FC, den Heijer M, Wetzels JF, Franzson L, Rafnar T, Kristjansson K, Bjornsdottir US, Eyjolfsson GI, Kiemeney LA, Kong A, Palsson R, Thorsteinsdottir U, Stefansson K
- Issue date: 2010 Jul 29
- Low prevalence of apolipoprotein L1 gene variants in Black South Africans with hypertension-attributed chronic kidney disease .
- Authors: Nqebelele NU, Dickens C, Dix-Peek T, Duarte R, Naicker S
- Issue date: 2019 Jan
- Assessing known chronic kidney disease associated genetic variants in Saudi Arabian populations.
- Authors: Cyrus C, Al-Mueilo S, Vatte C, Chathoth S, Li YR, Qutub H, Al Ali R, Al-Muhanna F, Lanktree MB, Alkharsah KR, Al-Rubaish A, Kim-Mozeleski B, Keating B, Al Ali A
- Issue date: 2018 Apr 17