6533b831fe1ef96bd1298e99
RESEARCH PRODUCT
Genome-wide association study of diabetic kidney disease highlights biology involved in renal basement membrane collagen
Jihwan ParkAngelo J. CantyRobert G. NelsonVita RovīteAnna MöllstenPeter RossingLinda T HirakiKatalin SusztakRonald KleinShelley B. BullJan SkupienJani K. HaukkaAndrew D. PatersonNiina SandholmCatherine GodsonAthina SpiliopoulouA. Peter MaxwellSuna Onengut-gumuscuTina CostacouHarvest F. GuHarvest F. GuAndrew P. BorightBarbara E.k. KleinRany M. SalemDavid-alexandre TrégouëtDavid-alexandre TrégouëtCarine M. Boustany-kariLina RadzevicieneRoss DoyleValma HarjutsaloHyun Min KangGareth J. MckayRachel G. MillerJose C. FlorezJennifer N. ToddJennifer N. ToddJennifer N. ToddMaria Luiza CaramoriLeif GroopLeif GroopEoin P. BrennanAndrzej KrolewskiMaria LajerRajasree MenonJelizaveta SokolovskaMichel MarreMichel MarreDarrel AndrewsDcctWei-min ChenEmma AhlqvistMaria HughesRaimund WeitgasserAndrew S.k. LiuJingchuan GuoEdita PrakapieneViji NairMatthias KretzlerBernhard PaulweberChen Di LiaoIan H. De BoerJing Jing CaoValdis PīrāgsGianpaolo ZerbiniGianpaolo ZerbiniMark I. MccarthyMark I. MccarthyStephen S. RichStephen S. RichTarunveer S. AhluwaliaJanet K. Snell-bergeonJoel N. HirschhornColin N. A. PalmerF MartinF MartinKerstin BrismarKerstin BrismarBeata GyorgyBeata GyorgyAdam M. SmilesDavid M. MaahsMichael MauerKristine E. LeeJoanne B. ColeJoanne B. ColeJoanne B. ColePer-henrik GroopRasa VerkauskieneMarcus G. PezzolesiXiaoyu GaoPaul M. MckeigueHenrik FalhammarHenrik FalhammarStuart J. McgurnaghanErkka ValoSilvia MaeastroniLars StechemesserHelen M. ColhounNatalie R. Van ZuydamNatalie R. Van ZuydamAmy J. McknightChengxiang QiuCarol ForsblomNicolae Mircea PanduruNicolae Mircea PanduruSamy Hadjadjsubject
0303 health sciencesGlomerular basement membraneRenal function030209 endocrinology & metabolismGenome-wide association studyBiologyurologic and male genital diseasesmedicine.diseaseBioinformatics3. Good healthMinor allele frequencyPathogenesis03 medical and health sciences0302 clinical medicinemedicine.anatomical_structureDiabetes mellitusAlbuminuriamedicineMissense mutationmedicine.symptom030304 developmental biologydescription
Diabetic kidney disease (DKD) is a heritable but poorly understood complication of diabetes. To identify genetic variants predisposing to DKD, we performed genome-wide association analyses in 19,406 individuals with type 1 diabetes (T1D) using a spectrum of DKD definitions basedon albuminuria and renal function. We identified 16 genome-wide significant loci. The variant with the strongest association (rs55703767) is a common missense mutation in the collagen type IV alpha 3 chain(COL4A3)gene, which encodes a major structural component of the glomerular basement membrane (GBM) implicated in heritable nephropathies. The rs55703767 minor allele (Asp326Tyr) is protective against several definitions of DKD, including albuminuria and end-stage renal disease. Three other loci are in or near genes with known or suggestive involvement in DKD(BMP7)or renal biology (COLEC11andDDR1). The 16 DKD-associated loci provide novel insights into the pathogenesis of DKD, identifying potential biological targets for prevention and treatment.
| year | journal | country | edition | language |
|---|---|---|---|---|
| 2018-12-19 |