Genetic loci associated with renal function measures and chronic kidney disease in children
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Genetic loci associated with renal function measures and chronic kidney disease in children : the Pediatric Investigation for Genetic Factors Linked with Renal Progression Consortium. / Wuttke, Matthias; Wong, Craig S; Wühl, Elke; Epting, Daniel; Luo, Li; Hoppmann, Anselm; Doyon, Anke; Li, Yong; Sözeri, Betül; Thurn, Daniela; Helmstädter, Martin; Huber, Tobias B; Blydt-Hansen, Tom D; Kramer-Zucker, Albrecht; Mehls, Otto; Melk, Anette; Querfeld, Uwe; Furth, Susan L; Warady, Bradley A; Schaefer, Franz; Köttgen, Anna; CKDGen Consortium.
in: NEPHROL DIAL TRANSPL, Jahrgang 31, Nr. 2, 02.2016, S. 262-9.Publikationen: SCORING: Beitrag in Fachzeitschrift/Zeitung › SCORING: Zeitschriftenaufsatz › Forschung › Begutachtung
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TY - JOUR
T1 - Genetic loci associated with renal function measures and chronic kidney disease in children
T2 - the Pediatric Investigation for Genetic Factors Linked with Renal Progression Consortium
AU - Wuttke, Matthias
AU - Wong, Craig S
AU - Wühl, Elke
AU - Epting, Daniel
AU - Luo, Li
AU - Hoppmann, Anselm
AU - Doyon, Anke
AU - Li, Yong
AU - Sözeri, Betül
AU - Thurn, Daniela
AU - Helmstädter, Martin
AU - Huber, Tobias B
AU - Blydt-Hansen, Tom D
AU - Kramer-Zucker, Albrecht
AU - Mehls, Otto
AU - Melk, Anette
AU - Querfeld, Uwe
AU - Furth, Susan L
AU - Warady, Bradley A
AU - Schaefer, Franz
AU - Köttgen, Anna
AU - CKDGen Consortium
N1 - © The Author 2015. Published by Oxford University Press on behalf of ERA-EDTA. All rights reserved.
PY - 2016/2
Y1 - 2016/2
N2 - BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.METHODS: The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular Comorbidity in Children with CKD (4C). Clean genotype data from > 10 million genotyped or imputed single-nucleotide polymorphisms (SNPs) were available for 1136 patients with measurements of serum creatinine at study enrollment. Genome-wide association studies were conducted to relate the SNPs to creatinine-based estimated glomerular filtration rate (eGFR crea) and proteinuria (urinary albumin- or protein-to-creatinine ratio ≥ 300 and ≥ 500 mg/g, respectively). In addition, European-ancestry PediGFR patients (cases) were compared with 1347 European-ancestry children without kidney disease (controls) to identify genetic variants associated with the presence of CKD.RESULTS: SNPs with suggestive association P-values < 1 × 10(-5) were identified in 10 regions for eGFR crea, four regions for proteinuria and six regions for CKD including some plausible biological candidates. No SNP was associated at genome-wide significance (P < 5 × 10(-8)). Investigation of the candidate genes for proteinuria in adults from the general population provided support for a region on chromosome 15 near RSL24D1/UNC13C/RAB27A. Conversely, targeted investigation of genes harboring GFR-associated variants in adults from the general population did not reveal significantly associated SNPs in children with CKD.CONCLUSIONS: Our findings suggest that larger collaborative efforts will be needed to draw reliable conclusions about the presence and identity of common variants associated with eGFR, proteinuria and CKD in pediatric populations.
AB - BACKGROUND: Chronic kidney disease (CKD) in children is characterized by rapid progression and a high incidence of end-stage renal disease and therefore constitutes an important health problem. While unbiased genetic screens have identified common risk variants influencing renal function and CKD in adults, the presence and identity of such variants in pediatric CKD are unknown.METHODS: The international Pediatric Investigation for Genetic Factors Linked with Renal Progression (PediGFR) Consortium comprises three pediatric CKD cohorts: Chronic Kidney Disease in Children (CKiD), Effect of Strict Blood Pressure Control and ACE Inhibition on the Progression of CRF in Pediatric Patients (ESCAPE) and Cardiovascular Comorbidity in Children with CKD (4C). Clean genotype data from > 10 million genotyped or imputed single-nucleotide polymorphisms (SNPs) were available for 1136 patients with measurements of serum creatinine at study enrollment. Genome-wide association studies were conducted to relate the SNPs to creatinine-based estimated glomerular filtration rate (eGFR crea) and proteinuria (urinary albumin- or protein-to-creatinine ratio ≥ 300 and ≥ 500 mg/g, respectively). In addition, European-ancestry PediGFR patients (cases) were compared with 1347 European-ancestry children without kidney disease (controls) to identify genetic variants associated with the presence of CKD.RESULTS: SNPs with suggestive association P-values < 1 × 10(-5) were identified in 10 regions for eGFR crea, four regions for proteinuria and six regions for CKD including some plausible biological candidates. No SNP was associated at genome-wide significance (P < 5 × 10(-8)). Investigation of the candidate genes for proteinuria in adults from the general population provided support for a region on chromosome 15 near RSL24D1/UNC13C/RAB27A. Conversely, targeted investigation of genes harboring GFR-associated variants in adults from the general population did not reveal significantly associated SNPs in children with CKD.CONCLUSIONS: Our findings suggest that larger collaborative efforts will be needed to draw reliable conclusions about the presence and identity of common variants associated with eGFR, proteinuria and CKD in pediatric populations.
KW - Adolescent
KW - Child
KW - Child, Preschool
KW - Disease Progression
KW - Europe
KW - Female
KW - Genetic Loci
KW - Genome-Wide Association Study
KW - Genotype
KW - Glomerular Filtration Rate
KW - Humans
KW - Infant
KW - Male
KW - Morbidity
KW - Polymorphism, Single Nucleotide
KW - Renal Insufficiency, Chronic
KW - Risk Factors
KW - Journal Article
KW - Research Support, N.I.H., Extramural
KW - Research Support, Non-U.S. Gov't
U2 - 10.1093/ndt/gfv342
DO - 10.1093/ndt/gfv342
M3 - SCORING: Journal article
C2 - 26420894
VL - 31
SP - 262
EP - 269
JO - NEPHROL DIAL TRANSPL
JF - NEPHROL DIAL TRANSPL
SN - 0931-0509
IS - 2
ER -