title: A meta-analysis of genome-wide data from five European isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level.
abstract: BACKGROUND
  Serum creatinine (S CR) is the most important biomarker for a quick and non-invasive assessment of kidney function in population-based surveys. A substantial proportion of the inter-individual variability in S CR level is explicable by genetic factors.
  
  
  METHODS
  We performed a meta-analysis of genome-wide association studies of S CR undertaken in five population isolates ('discovery cohorts'), all of which are part of the European Special Population Network (EUROSPAN) project. Genes showing the strongest evidence for an association with SCR (candidate loci) were replicated in two additional population-based samples ('replication cohorts').
  
  
  RESULTS
  After the discovery meta-analysis, 29 loci were selected for replication. Association between SCR level and polymorphisms in the collagen type XXII alpha 1 (COL22A1) gene, on chromosome 8, and in the synaptotagmin-1 (SYT1) gene, on chromosome 12, were successfully replicated in the replication cohorts (p value = 1.0 x 10(-6) and 1.7 x 10(-4), respectively). Evidence of association was also found for polymorphisms in a locus including the gamma-aminobutyric acid receptor rho-2 (GABRR2) gene and the ubiquitin-conjugating enzyme E2-J1 (UBE2J1) gene (replication p value = 3.6 x 10(-3)). Previously reported findings, associating glomerular filtration rate with SNPs in the uromodulin (UMOD) gene and in the schroom family member 3 (SCHROOM3) gene were also replicated.
  
  
  CONCLUSIONS
  While confirming earlier results, our study provides new insights in the understanding of the genetic basis of serum creatinine regulatory processes. In particular, the association with the genes SYT1 and GABRR2 corroborate previous findings that highlighted a possible role of the neurotransmitters GABAA receptors in the regulation of the glomerular basement membrane and a possible interaction between GABAA receptors and synaptotagmin-I at the podocyte level.
authors.affiliation: Institute of Genetic Medicine, European Academy Bozen/Bolzano (EURAC), Bolzano, Italy. cristian.pattaro@eurac.edu
authors.forename: Cristian
authors.initials: C
authors.lastname: Pattaro
authors.forename: Alessandro
authors.initials: A
authors.lastname: De Grandi
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Andre
authors.initials: A
authors.lastname: Franke
authors.forename: Yurii S
authors.initials: YS
authors.lastname: Aulchenko
authors.forename: Asa
authors.initials: A
authors.lastname: Johansson
authors.forename: Sarah H
authors.initials: SH
authors.lastname: Wild
authors.forename: Scott A
authors.initials: SA
authors.lastname: Melville
authors.forename: Aaron
authors.initials: A
authors.lastname: Isaacs
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: David
authors.initials: D
authors.lastname: Ellinghaus
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolcic
authors.forename: Ute
authors.initials: U
authors.lastname: Nöthlings
authors.forename: Lina
authors.initials: L
authors.lastname: Zgaga
authors.forename: Tatijana
authors.initials: T
authors.lastname: Zemunik
authors.forename: Carsten
authors.initials: C
authors.lastname: Gnewuch
authors.forename: Stefan
authors.initials: S
authors.lastname: Schreiber
authors.forename: Susan
authors.initials: S
authors.lastname: Campbell
authors.forename: Nick
authors.initials: N
authors.lastname: Hastie
authors.forename: Mladen
authors.initials: M
authors.lastname: Boban
authors.forename: Thomas
authors.initials: T
authors.lastname: Meitinger
authors.forename: Ben A
authors.initials: BA
authors.lastname: Oostra
authors.forename: Peter
authors.initials: P
authors.lastname: Riegler
authors.forename: Cosetta
authors.initials: C
authors.lastname: Minelli
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Cornelia M
authors.initials: CM
authors.lastname: van Duijn
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Michael
authors.initials: M
authors.lastname: Krawczak
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Peter P
authors.initials: PP
authors.lastname: Pramstaller
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001324:Autoantigens / Q000235:genetics*; D002881:Chromosomes, Human, Pair 12 / Q000235:genetics; D002898:Chromosomes, Human, Pair 8 / Q000235:genetics; D015331:Cohort Studies; D003404:Creatinine / Q000097:blood*; D017523:Croatia; D055106:Genome-Wide Association Study; D005858:Germany; D006801:Humans; D008875:Middle Aged; D024041:Non-Fibrillar Collagens / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011963:Receptors, GABA-A / Q000235:genetics*; D015203:Reproducibility of Results; D050863:Synaptotagmin I / Q000235:genetics*; D044465:White People / Q000235:genetics*; D055815:Young Adult; D000097805:Collagen Type XVII
chemical_list: D001324:Autoantigens; D003404:Creatinine; D024041:Non-Fibrillar Collagens; D011963:Receptors, GABA-A; D050863:Synaptotagmin I; D000097805:Collagen Type XVII; C106350:GABRR2 protein, human