title: Meta-analysis of genome-wide linkage scans for renal function traits.
abstract: BACKGROUND
  Several genome scans have explored the linkage of chronic kidney disease phenotypes to chromosomic regions with disparate results. Genome scan meta-analysis (GSMA) is a quantitative method to synthesize linkage results from independent studies and assess their concordance.
  
  
  METHODS
  We searched PubMed to identify genome linkage analyses of renal function traits in humans, such as estimated glomerular filtration rate (GFR), albuminuria, serum creatinine concentration and creatinine clearance. We contacted authors for numerical data and extracted information from individual studies. We applied the GSMA nonparametric approach to combine results across 14 linkage studies for GFR, 11 linkage studies for albumin creatinine ratio, 11 linkage studies for serum creatinine and 4 linkage studies for creatinine clearance.
  
  
  RESULTS
  No chromosomal region reached genome-wide statistical significance in the main analysis which included all scans under each phenotype; however, regions on Chromosomes 7, 10 and 16 reached suggestive significance for linkage to two or more phenotypes. Subgroup analyses by disease status or ethnicity did not yield additional information.
  
  
  CONCLUSIONS
  While heterogeneity across populations, methodologies and study designs likely explain this lack of agreement, it is possible that linkage scan methodologies lack the resolution for investigating complex traits. Combining family-based linkage studies with genome-wide association studies may be a powerful approach to detect private mutations contributing to complex renal phenotypes.
authors.affiliation: Division of Nephrology, Tufts Medical Center, Boston, MA, USA.
authors.forename: Madhumathi
authors.initials: M
authors.lastname: Rao
authors.forename: Amy K
authors.initials: AK
authors.lastname: Mottl
authors.forename: Shelley A
authors.initials: SA
authors.lastname: Cole
authors.forename: Jason G
authors.initials: JG
authors.lastname: Umans
authors.forename: Barry I
authors.initials: BI
authors.lastname: Freedman
authors.forename: Donald W
authors.initials: DW
authors.lastname: Bowden
authors.forename: Carl D
authors.initials: CD
authors.lastname: Langefeld
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Qiong
authors.initials: Q
authors.lastname: Yang
authors.forename: Adrienne
authors.initials: A
authors.lastname: Cupples
authors.forename: Sudha K
authors.initials: SK
authors.lastname: Iyengar
authors.forename: Steven C
authors.initials: SC
authors.lastname: Hunt
authors.forename: Thomas A
authors.initials: TA
authors.lastname: Trikalinos
mesh_terms: D005260:Female; D008040:Genetic Linkage; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D055106:Genome-Wide Association Study / Q000379:methods*; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D007676:Kidney Failure, Chronic / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics*; D008297:Male; D012680:Sensitivity and Specificity