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Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function

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Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

Vyšlo v časopise: Genome-Wide Association and Functional Follow-Up Reveals New Loci for Kidney Function. PLoS Genet 8(3): e32767. doi:10.1371/journal.pgen.1002584
Kategorie: Research Article
prolekare.web.journal.doi_sk: https://doi.org/10.1371/journal.pgen.1002584

Souhrn

Chronic kidney disease (CKD) is an important public health problem with a genetic component. We performed genome-wide association studies in up to 130,600 European ancestry participants overall, and stratified for key CKD risk factors. We uncovered 6 new loci in association with estimated glomerular filtration rate (eGFR), the primary clinical measure of CKD, in or near MPPED2, DDX1, SLC47A1, CDK12, CASP9, and INO80. Morpholino knockdown of mpped2 and casp9 in zebrafish embryos revealed podocyte and tubular abnormalities with altered dextran clearance, suggesting a role for these genes in renal function. By providing new insights into genes that regulate renal function, these results could further our understanding of the pathogenesis of CKD.

Zdroje

1. Meguid El NahasABelloAK 2005 Chronic kidney disease: The global challenge. Lancet 365 9456 331 340

2. ImaiEMatsuoS 2008 Chronic kidney disease in asia. Lancet 371 9631 2147 2148

3. CoreshJSelvinEStevensLAManziJKusekJW 2007 Prevalence of chronic kidney disease in the united states. JAMA 298 17 2038 2047

4. LeveyASde JongPECoreshJEl NahasMAstorBC 2011 The definition, classification, and prognosis of chronic kidney disease: A KDIGO controversies conference report. Kidney Int 80 1 17 28

5. van der VeldeMMatsushitaKCoreshJAstorBCWoodwardM 2011 Lower estimated glomerular filtration rate and higher albuminuria are associated with all-cause and cardiovascular mortality. A collaborative meta-analysis of high-risk population cohorts. Kidney Int 79 12 1341 1352

6. GansevoortRTMatsushitaKvan der VeldeMAstorBCWoodwardM 2011 Lower estimated GFR and higher albuminuria are associated with adverse kidney outcomes. A collaborative meta-analysis of general and high-risk population cohorts. Kidney Int 80 1 93 104

7. AstorBCMatsushitaKGansevoortRTvan der VeldeMWoodwardM 2011 Lower estimated glomerular filtration rate and higher albuminuria are associated with mortality and end-stage renal disease. A collaborative meta-analysis of kidney disease population cohorts. Kidney Int 79 12 1331 1340

8. KottgenAGlazerNLDehghanAHwangSJKatzR 2009 Multiple loci associated with indices of renal function and chronic kidney disease. Nat Genet 41 6 712 717

9. KottgenAPattaroCBogerCAFuchsbergerCOldenM 2010 New loci associated with kidney function and chronic kidney disease. Nat Genet 42 5 376 384

10. ChambersJCZhangWLordGMvan der HarstPLawlorDA 2010 Genetic loci influencing kidney function and chronic kidney disease. Nat Genet 42 5 373 375

11. GudbjartssonDFHolmHIndridasonOSThorleifssonGEdvardssonV 2010 Association of variants at UMOD with chronic kidney disease and kidney stones-role of age and comorbid diseases. PLoS Genet 6 e1001039 doi:10.1371/journal.pgen.1001039

12. LiuCTGarnaasMKTinAKottgenAFranceschiniN 2011 Genetic association for renal traits among participants of african ancestry reveals new loci for renal function. PLoS Genet 7 e1002264 doi:10.1371/journal.pgen.1002264

13. AllanLAClarkePR 2009 Apoptosis and autophagy: Regulation of caspase-9 by phosphorylation. FEBS J 276 21 6063 6073

14. GobeGCraneD 2010 Mitochondria, reactive oxygen species and cadmium toxicity in the kidney. Toxicol Lett 198 1 49 55

15. DrummondIAMajumdarAHentschelHElgerMSolnica-KrezelL 1998 Early development of the zebrafish pronephros and analysis of mutations affecting pronephric function. Development 125 23 4655 4667

16. Kramer-ZuckerAGWiessnerSJensenAMDrummondIA 2005 Organization of the pronephric filtration apparatus in zebrafish requires nephrin, podocin and the FERM domain protein mosaic eyes. Dev Biol 285 2 316 329

17. WingertRASelleckRYuJSongHDChenZ 2007 The cdx genes and retinoic acid control the positioning and segmentation of the zebrafish pronephros. PLoS Genet 3 e189 doi:10.1371/journal.pgen.0030189

18. TyagiRShenoyARVisweswariahSS 2009 Characterization of an evolutionarily conserved metallophosphoesterase that is expressed in the fetal brain and associated with the WAGR syndrome. J Biol Chem 284 8 5217 5228

19. SchwartzFEisenmanRKnollJGesslerMBrunsG 1995 cDNA sequence, genomic organization, and evolutionary conservation of a novel gene from the WAGR region. Genomics 29 2 526 532

20. BogerCAChenMHTinAOldenMKottgenA 2011 CUBN is a gene locus for albuminuria. J Am Soc Nephrol 22 3 555 570

21. EhretGBMunroePBRiceKMBochudM  The International Consortium for Blood Pressure Genome-Wide Association Studies 2011 Genetic variants in novel pathways influence blood pressure and cardiovascular disease risk. Nature 478 7367 103 109

22. SchunkertHKonigIRKathiresanSReillyMPAssimesTL 2011 Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease. Nat Genet 43 4 333 338

23. PattaroCDe GrandiAVitartVHaywardCFrankeA 2010 A meta-analysis of genome-wide data from five european isolates reveals an association of COL22A1, SYT1, and GABRR2 with serum creatinine level. BMC Med Genet 11 41

24. FoxCSLarsonMGLeipEPCulletonBWilsonPW 2004 Predictors of new-onset kidney disease in a community-based population. JAMA 291 7 844 850

25. CoreshJAstorBCMcQuillanGKusekJGreeneT 2002 Calibration and random variation of the serum creatinine assay as critical elements of using equations to estimate glomerular filtration rate. Am J Kidney Dis 39 5 920 929

26. LeveyASBoschJPLewisJBGreeneTRogersN 1999 A more accurate method to estimate glomerular filtration rate from serum creatinine: A new prediction equation. modification of diet in renal disease study group. Ann Intern Med 130 6 461 470

27. StevensLACoreshJSchmidCHFeldmanHIFroissartM 2008 Estimating GFR using serum cystatin C alone and in combination with serum creatinine: A pooled analysis of 3,418 individuals with CKD. Am J Kidney Dis 51 3 395 406

28. National Kidney Foundation. 2002 K/DOQI clinical practice guidelines for chronic kidney disease: Evaluation, classification, and stratification. Am J Kidney Dis 39 2 Suppl 1 S1 266

29. FuchsbergerCTaliunDPramstallerPPPattaroC  on behalf of the CKDGen consortium 2011 GWAtoolbox: An R package for fast quality control and handling of GWAS meta-analysis data. Bioinformatics 10.1093/bioinformatics/btr679

30. WillerCJLiYAbecasisGR 2010 METAL: Fast and efficient meta-analysis of genomewide association scans. Bioinformatics 26 17 2190 2191

31. DevlinBRoederK 1999 Genomic control for association studies. Biometrics 55 4 997 1004

32. Pe'erIYelenskyRAltshulerDDalyMJ 2008 Estimation of the multiple testing burden for genomewide association studies of nearly all common variants. Genet Epidemiol 32 4 381 385

33. CohenA 1983 Comparing regression coefficients across subsamples. Sociol Methods Res 12 77 94

34. StoreyJDTibshiraniR 2003 Statistical significance for genomewide studies. Proc Natl Acad Sci U S A 100 16 9440 9445

35. HigginsJPThompsonSGDeeksJJAltmanDG 2003 Measuring inconsistency in meta-analyses. BMJ 327 7414 557 560

36. GoringHHCurranJEJohnsonMPDyerTDCharlesworthJ 2007 Discovery of expression QTLs using large-scale transcriptional profiling in human lymphocytes. Nat Genet 39 10 1208 1216

37. IdaghdourYCzikaWShiannaKVLeeSHVisscherPM 2010 Geographical genomics of human leukocyte gene expression variation in southern morocco. Nat Genet 42 1 62 67

38. HeapGATrynkaGJansenRCBruinenbergMSwertzMA 2009 Complex nature of SNP genotype effects on gene expression in primary human leucocytes. BMC Med Genomics 2 1

39. DixonALLiangLMoffattMFChenWHeathS 2007 A genome-wide association study of global gene expression. Nat Genet 39 10 1202 1207

40. StrangerBENicaACForrestMSDimasABirdCP 2007 Population genomics of human gene expression. Nat Genet 39 10 1217 1224

41. KwanTBenovoyDDiasCGurdSProvencherC 2008 Genome-wide analysis of transcript isoform variation in humans. Nat Genet 40 2 225 231

42. HeinzenELGeDCroninKDMaiaJMShiannaKV 2008 Tissue-specific genetic control of splicing: Implications for the study of complex traits. PLoS Biol 6 e1 doi:10.1371/journal.pbio.1000001

43. ZellerTWildPSzymczakSRotivalMSchillertA 2010 Genetics and beyond—the transcriptome of human monocytes and disease susceptibility. PLoS ONE 5 e10693 doi:10.1371/journal.pone.0010693

44. EmilssonVThorleifssonGZhangBLeonardsonASZinkF 2008 Genetics of gene expression and its effect on disease. Nature 452 7186 423 428

45. GreenawaltDMDobrinRChudinEHatoumIJSuverC 2011 A survey of the genetics of stomach, liver, and adipose gene expression from a morbidly obese cohort. Genome Res 21 7 1008 1016

46. WebsterJAGibbsJRClarkeJRayMZhangW 2009 Genetic control of human brain transcript expression in alzheimer disease. Am J Hum Genet 84 4 445 458

47. SchadtEEMolonyCChudinEHaoKYangX 2008 Mapping the genetic architecture of gene expression in human liver. PLoS Biol 6 e107 doi:10.1371/journal.pbio.0060107

48. GrundbergEKwanTGeBLamKCKokaV 2009 Population genomics in a disease targeted primary cell model. Genome Res 19 11 1942 1952

49. DingJGudjonssonJELiangLStuartPELiY 2010 Gene expression in skin and lymphoblastoid cells: Refined statistical method reveals extensive overlap in cis-eQTL signals. Am J Hum Genet 87 6 779 789

50. DimasASDeutschSStrangerBEMontgomerySBBorelC 2009 Common regulatory variation impacts gene expression in a cell type-dependent manner. Science 325 5945 1246 1250

51. RodwellGESonuRZahnJMLundJWilhelmyJ 2004 A transcriptional profile of aging in the human kidney. PLoS Biol 2 e427 doi:10.1371/journal.pbio.0020427

52. WheelerHEMetterEJTanakaTAbsherDHigginsJ 2009 Sequential use of transcriptional profiling, expression quantitative trait mapping, and gene association implicates MMP20 in human kidney aging. PLoS Genet 5 e1000685 doi:10.1371/journal.pgen.1000685

53. JohnsonADHandsakerREPulitSLNizzariMMO'DonnellCJ 2008 SNAP: A web-based tool for identification and annotation of proxy SNPs using HapMap. Bioinformatics 24 24 2938 2939

54. SidiSSandaTKennedyRDHagenATJetteCA 2008 Chk1 suppresses a caspase-2 apoptotic response to DNA damage that bypasses p53, bcl-2, and caspase-3. Cell 133 5 864 877

55. HentschelDMMengelMBoehmeLLiebschFAlbertinC 2007 Rapid screening of glomerular slit diaphragm integrity in larval zebrafish. Am J Physiol Renal Physiol 293 5 F1746 50

56. HentschelDMParkKMCilentiLZervosASDrummondI 2005 Acute renal failure in zebrafish: A novel system to study a complex disease. Am J Physiol Renal Physiol 288 5 F923 9

57. PruimRJWelchRPSannaSTeslovichTMChinesPS 2010 LocusZoom: Regional visualization of genome-wide association scan results. Bioinformatics 26 18 2336 2337

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2012 Číslo 3
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