title: Genetic association and gene-gene interaction analyses in African American dialysis patients with nondiabetic nephropathy.
abstract: BACKGROUND
  African Americans have increased susceptibility to nondiabetic nephropathy relative to European Americans.
  
  
  METHODS
  Follow-up of a pooled genome-wide association study (GWAS) in African American dialysis patients with nondiabetic nephropathy; novel gene-gene interaction analyses.
  
  
  METHODS
  Wake Forest sample: 962 African American nondiabetic nephropathy cases, 931 non-nephropathy controls. Replication sample: 668 Family Investigation of Nephropathy and Diabetes (FIND) African American nondiabetic nephropathy cases, 804 non-nephropathy controls.
  
  
  METHODS
  Individual genotyping of top 1,420 pooled GWAS-associated single-nucleotide polymorphisms (SNPs) and 54 SNPs in 6 nephropathy susceptibility genes.
  
  
  RESULTS
  APOL1 genetic association and additional candidate susceptibility loci interacting with or independently from APOL1.
  
  
  RESULTS
  The strongest GWAS associations included 2 noncoding APOL1 SNPs, rs2239785 (OR, 0.33; dominant; P = 5.9 × 10(-24)) and rs136148 (OR, 0.54; additive; P = 1.1 × 10(-7)) with replication in FIND (P = 5.0 × 10(-21) and 1.9 × 10(-05), respectively). rs2239785 remained associated significantly after controlling for the APOL1 G1 and G2 coding variants. Additional top hits included a CFH SNP (OR from meta-analysis in the 3,367 African American cases and controls, 0.81; additive; P = 6.8 × 10(-4)). The 1,420 SNPs were tested for interaction with APOL1 G1 and G2 variants. Several interactive SNPs were detected; the most significant was rs16854341 in the podocin gene (NPHS2; P = 0.0001).
  
  
  CONCLUSIONS
  Nonpooled GWASs have not been performed in African American patients with nondiabetic nephropathy.
  
  
  CONCLUSIONS
  This follow-up of a pooled GWAS provides additional and independent evidence that APOL1 variants contribute to nondiabetic nephropathy in African Americans and identified additional associated and interactive nondiabetic nephropathy susceptibility genes.
authors: Wake Forest School of Medicine, Winston-Salem, NC, USA.
authors: Meredith A
authors: MA
authors: Bostrom
authors: W H Linda
authors: WH
authors: Kao
authors: Man
authors: M
authors: Li
authors: Hanna E
authors: HE
authors: Abboud
authors: Sharon G
authors: SG
authors: Adler
authors: Sudha K
authors: SK
authors: Iyengar
authors: Paul L
authors: PL
authors: Kimmel
authors: Robert L
authors: RL
authors: Hanson
authors: Susanne B
authors: SB
authors: Nicholas
authors: Rebekah S
authors: RS
authors: Rasooly
authors: John R
authors: JR
authors: Sedor
authors: Josef
authors: J
authors: Coresh
authors: Orly F
authors: OF
authors: Kohn
authors: David J
authors: DJ
authors: Leehey
authors: Denyse
authors: D
authors: Thornley-Brown
authors: Erwin P
authors: EP
authors: Bottinger
authors: Michael S
authors: MS
authors: Lipkowitz
authors: Lucy A
authors: LA
authors: Meoni
authors: Michael J
authors: MJ
authors: Klag
authors: Lingyi
authors: L
authors: Lu
authors: Pamela J
authors: PJ
authors: Hicks
authors: Carl D
authors: CD
authors: Langefeld
authors: Rulan S
authors: RS
authors: Parekh
authors: Donald W
authors: DW
authors: Bowden
authors: Barry I
authors: BI
authors: Freedman
mesh_terms: D000328:Adult; D001741:Black or African American / Q000235:genetics*; D000368:Aged; D000075944:Apolipoprotein L1; D001053:Apolipoproteins / Q000235:genetics; D016022:Case-Control Studies; D004843:Epistasis, Genetic / Q000235:genetics*; D005260:Female; D005500:Follow-Up Studies; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease / Q000208:ethnology / Q000235:genetics; D005838:Genotype; D006801:Humans; D015994:Incidence; D047908:Intracellular Signaling Peptides and Proteins / Q000235:genetics; D007674:Kidney Diseases / Q000208:ethnology* / Q000235:genetics* / Q000628:therapy; D008075:Lipoproteins, HDL / Q000235:genetics; D008297:Male; D008565:Membrane Proteins / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D006435:Renal Dialysis
chemical_list: C108666:APOL1 protein, human; D000075944:Apolipoprotein L1; D001053:Apolipoproteins; D047908:Intracellular Signaling Peptides and Proteins; D008075:Lipoproteins, HDL; D008565:Membrane Proteins; C407223:NPHS2 protein