title: Overlap between common genetic polymorphisms underpinning kidney traits and cardiovascular disease phenotypes: the CKDGen consortium.
abstract: BACKGROUND
  Chronic kidney disease is associated with cardiovascular disease. We tested for evidence of a shared genetic basis to these traits.
  
  
  METHODS
  We conducted 2 targeted analyses. First, we examined whether known single-nucleotide polymorphisms (SNPs) underpinning kidney traits were associated with a series of vascular phenotypes. Additionally, we tested whether vascular SNPs were associated with markers of kidney damage. Significance was set to 1.5×10(-4) (0.05/325 tests).
  
  
  METHODS
  Vascular outcomes were analyzed in participants from the AortaGen (20,634), CARDIoGRAM (86,995), CHARGE Eye (15,358), CHARGE IMT (31,181), ICBP (69,395), and NeuroCHARGE (12,385) consortia. Tests for kidney outcomes were conducted in up to 67,093 participants from the CKDGen consortium.
  
  
  METHODS
  We used 19 kidney SNPs and 64 vascular SNPs.
  
  
  METHODS
  Vascular outcomes tested were blood pressure, coronary artery disease, carotid intima-media thickness, pulse wave velocity, retinal venular caliber, and brain white matter lesions. Kidney outcomes were estimated glomerular filtration rate and albuminuria.
  
  
  RESULTS
  In general, we found that kidney disease variants were not associated with vascular phenotypes (127 of 133 tests were nonsignificant). The one exception was rs653178 near SH2B3 (SH2B adaptor protein 3), which showed direction-consistent association with systolic (P = 9.3 ×10(-10)) and diastolic (P = 1.6 ×10(-14)) blood pressure and coronary artery disease (P = 2.2 ×10(-6)), all previously reported. Similarly, the 64 SNPs associated with vascular phenotypes were not associated with kidney phenotypes (187 of 192 tests were nonsignificant), with the exception of 2 high-correlated SNPs at the SH2B3 locus (P = 1.06 ×10(-07) and P = 7.05 ×10(-08)).
  
  
  CONCLUSIONS
  The combined effect size of the SNPs for kidney and vascular outcomes may be too low to detect shared genetic associations.
  
  
  CONCLUSIONS
  Overall, although we confirmed one locus (SH2B3) as associated with both kidney and cardiovascular disease, our primary findings suggest that there is little overlap between kidney and cardiovascular disease risk variants in the overall population. The reciprocal risks of kidney and cardiovascular disease may not be genetically mediated, but rather a function of the disease milieu itself.
authors.affiliation: National Heart, Lung, and Blood Institute's Framingham Heart Study, Framingham, MA 01702, USA.
authors.forename: Matthias
authors.initials: M
authors.lastname: Olden
authors.forename: Alexander
authors.initials: A
authors.lastname: Teumer
authors.forename: Murielle
authors.initials: M
authors.lastname: Bochud
authors.forename: Cristian
authors.initials: C
authors.lastname: Pattaro
authors.forename: Anna
authors.initials: A
authors.lastname: Köttgen
authors.forename: Stephen T
authors.initials: ST
authors.lastname: Turner
authors.forename: Rainer
authors.initials: R
authors.lastname: Rettig
authors.forename: Ming-Huei
authors.initials: MH
authors.lastname: Chen
authors.forename: Abbas
authors.initials: A
authors.lastname: Dehghan
authors.forename: Francois
authors.initials: F
authors.lastname: Bastardot
authors.forename: Reinhold
authors.initials: R
authors.lastname: Schmidt
authors.forename: Peter
authors.initials: P
authors.lastname: Vollenweider
authors.forename: Heribert
authors.initials: H
authors.lastname: Schunkert
authors.forename: Muredach P
authors.initials: MP
authors.lastname: Reilly
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Lenore J
authors.initials: LJ
authors.lastname: Launer
authors.forename: Germaine C
authors.initials: GC
authors.lastname: Verwoert
authors.forename: Gary F
authors.initials: GF
authors.lastname: Mitchell
authors.forename: Joshua C
authors.initials: JC
authors.lastname: Bis
authors.forename: Christopher J
authors.initials: CJ
authors.lastname: O'Donnell
authors.forename: Ching-Yu
authors.initials: CY
authors.lastname: Cheng
authors.forename: Xueling
authors.initials: X
authors.lastname: Sim
authors.forename: David S
authors.initials: DS
authors.lastname: Siscovick
authors.forename: Josef
authors.initials: J
authors.lastname: Coresh
authors.forename: W H Linda
authors.initials: WH
authors.lastname: Kao
authors.forename: Caroline S
authors.initials: CS
authors.lastname: Fox
authors.forename: Conall M
authors.initials: CM
authors.lastname: O'Seaghdha
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000328:Adult; D000368:Aged; D001794:Blood Pressure / Q000235:genetics; D002318:Cardiovascular Diseases / Q000235:genetics*; D059168:Carotid Intima-Media Thickness; D005260:Female; D055106:Genome-Wide Association Study; D005919:Glomerular Filtration Rate / Q000235:genetics; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics; D051436:Renal Insufficiency, Chronic / Q000235:genetics*
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; C490778:SH2B3 protein, human