#PAGE_PARAMS# #ADS_HEAD_SCRIPTS# #MICRODATA#
preLekára.sk / Odborné časopisy / PLOS Genetics / 2012 - 3

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

English version České info

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

Štítky
Genetika Reprodukčná medicína
Článek Comprehensive Research Synopsis and Systematic Meta-Analyses in Parkinson's Disease Genetics: The PDGene Database
Článek Genomic Analysis of the Hydrocarbon-Producing, Cellulolytic, Endophytic Fungus
Článek Networks of Neuronal Genes Affected by Common and Rare Variants in Autism Spectrum Disorders
Článek Akirin Links Twist-Regulated Transcription with the Brahma Chromatin Remodeling Complex during Embryogenesis
Článek Too Much Cleavage of Cyclin E Promotes Breast Tumorigenesis
Článek Imprinted Genes … and the Number Is?
Článek Genetic Architecture of Highly Complex Chemical Resistance Traits across Four Yeast Strains
Článek Exploring the Complexity of the HIV-1 Fitness Landscape
Článek MNS1 Is Essential for Spermiogenesis and Motile Ciliary Functions in Mice
Článek A Fundamental Regulatory Mechanism Operating through OmpR and DNA Topology Controls Expression of Pathogenicity Islands SPI-1 and SPI-2
Článek Evidence for Positive Selection on a Number of MicroRNA Regulatory Interactions during Recent Human Evolution
Článek Variation in Modifies Risk of Neonatal Intestinal Obstruction in Cystic Fibrosis
Článek PIF4–Mediated Activation of Expression Integrates Temperature into the Auxin Pathway in Regulating Hypocotyl Growth
Článek Critical Evaluation of Imprinted Gene Expression by RNA–Seq: A New Perspective
Článek A Meta-Analysis and Genome-Wide Association Study of Platelet Count and Mean Platelet Volume in African Americans
Článek Mouse Genetics Suggests Cell-Context Dependency for Myc-Regulated Metabolic Enzymes during Tumorigenesis
Článek Transcriptional Control in Cardiac Progenitors: Tbx1 Interacts with the BAF Chromatin Remodeling Complex and Regulates
Článek Synthetic Lethality of Cohesins with PARPs and Replication Fork Mediators
Článek APOBEC3G-Induced Hypermutation of Human Immunodeficiency Virus Type-1 Is Typically a Discrete “All or Nothing” Phenomenon
Článek Interpreting Meta-Analyses of Genome-Wide Association Studies
Článek Error-Prone ZW Pairing and No Evidence for Meiotic Sex Chromosome Inactivation in the Chicken Germ Line
Článek -Dependent Chemosensory Functions Contribute to Courtship Behavior in
Článek Diverse Forms of Splicing Are Part of an Evolving Autoregulatory Circuit
Článek Phenotypic Plasticity of the Drosophila Transcriptome
Článek Physiological Notch Signaling Maintains Bone Homeostasis via RBPjk and Hey Upstream of NFATc1
Článek Precocious Metamorphosis in the Juvenile Hormone–Deficient Mutant of the Silkworm,
Článek Igf1r Signaling Is Indispensable for Preimplantation Development and Is Activated via a Novel Function of E-cadherin
Článek Accurate Prediction of Inducible Transcription Factor Binding Intensities In Vivo
Článek Mitochondrial Oxidative Stress Alters a Pathway in Strongly Resembling That of Bile Acid Biosynthesis and Secretion in Vertebrates
Článek Mammalian Neurogenesis Requires Treacle-Plk1 for Precise Control of Spindle Orientation, Mitotic Progression, and Maintenance of Neural Progenitor Cells
Článek Tcf7 Is an Important Regulator of the Switch of Self-Renewal and Differentiation in a Multipotential Hematopoietic Cell Line
Článek REST–Mediated Recruitment of Polycomb Repressor Complexes in Mammalian Cells
Článek Intronic -Regulatory Modules Mediate Tissue-Specific and Microbial Control of / Transcription
Článek Age-Dependent Brain Gene Expression and Copy Number Anomalies in Autism Suggest Distinct Pathological Processes at Young Versus Mature Ages
Článek A Genome-Wide Association Study Identifies Variants Underlying the Shade Avoidance Response
Článek -by- Regulatory Divergence Causes the Asymmetric Lethal Effects of an Ancestral Hybrid Incompatibility Gene
Článek A Natural System of Chromosome Transfer in
Článek Cell Size and the Initiation of DNA Replication in Bacteria
Článek Probing the Informational and Regulatory Plasticity of a Transcription Factor DNA–Binding Domain
Článek Repression of Germline RNAi Pathways in Somatic Cells by Retinoblastoma Pathway Chromatin Complexes
Článek Temporal Transcriptional Profiling of Somatic and Germ Cells Reveals Biased Lineage Priming of Sexual Fate in the Fetal Mouse Gonad
Článek Rapid Analysis of Genome Rearrangements by Multiplex Ligation–Dependent Probe Amplification
Článek Metabolic Profiling of a Mapping Population Exposes New Insights in the Regulation of Seed Metabolism and Seed, Fruit, and Plant Relations
Článek The Atypical Calpains: Evolutionary Analyses and Roles in Cellular Degeneration
Článek The Silkworm Coming of Age—Early
Článek Development of a Panel of Genome-Wide Ancestry Informative Markers to Study Admixture Throughout the Americas
Článek Balanced Codon Usage Optimizes Eukaryotic Translational Efficiency
Článek The Min System and Nucleoid Occlusion Are Not Required for Identifying the Division Site in but Ensure Its Efficient Utilization
Článek Neurobeachin, a Regulator of Synaptic Protein Targeting, Is Associated with Body Fat Mass and Feeding Behavior in Mice and Body-Mass Index in Humans
Článek Statistical Analysis of Readthrough Levels for Nonsense Mutations in Mammalian Cells Reveals a Major Determinant of Response to Gentamicin
Článek Gene Reactivation by 5-Aza-2′-Deoxycytidine–Induced Demethylation Requires SRCAP–Mediated H2A.Z Insertion to Establish Nucleosome Depleted Regions
Článek The miR-35-41 Family of MicroRNAs Regulates RNAi Sensitivity in
Článek Genetic Basis of Hidden Phenotypic Variation Revealed by Increased Translational Readthrough in Yeast
Článek An Alu Element–Associated Hypermethylation Variant of the Gene Is Associated with Childhood Obesity
Článek Modelling Human Regulatory Variation in Mouse: Finding the Function in Genome-Wide Association Studies and Whole-Genome Sequencing
Článek Novel Loci for Adiponectin Levels and Their Influence on Type 2 Diabetes and Metabolic Traits: A Multi-Ethnic Meta-Analysis of 45,891 Individuals
Článek Polycomb-Like 3 Promotes Polycomb Repressive Complex 2 Binding to CpG Islands and Embryonic Stem Cell Self-Renewal
Článek Insulin/IGF-1 and Hypoxia Signaling Act in Concert to Regulate Iron Homeostasis in
Článek EMF1 and PRC2 Cooperate to Repress Key Regulators of Arabidopsis Development
Článek Three Essential Ribonucleases—RNase Y, J1, and III—Control the Abundance of a Majority of mRNAs
Článek Contrasted Patterns of Molecular Evolution in Dominant and Recessive Self-Incompatibility Haplotypes in
Článek A Machine Learning Approach for Identifying Novel Cell Type–Specific Transcriptional Regulators of Myogenesis
Článek Genomic Tools for Evolution and Conservation in the Chimpanzee: Is a Genetically Distinct Population
Článek Nos2 Inactivation Promotes the Development of Medulloblastoma in Mice by Deregulation of Gap43–Dependent Granule Cell Precursor Migration
Článek Intracranial Aneurysm Risk Locus 5q23.2 Is Associated with Elevated Systolic Blood Pressure
Článek Heritability and Genetic Correlations Explained by Common SNPs for Metabolic Syndrome Traits
Článek A Genome-Wide Association Study of Nephrolithiasis in the Japanese Population Identifies Novel Susceptible Loci at 5q35.3, 7p14.3, and 13q14.1
Článek DNA Damage in Nijmegen Breakage Syndrome Cells Leads to PARP Hyperactivation and Increased Oxidative Stress
Článek DNA Resection at Chromosome Breaks Promotes Genome Stability by Constraining Non-Allelic Homologous Recombination
Článek Genetic Analysis of Floral Symmetry in Van Gogh's Sunflowers Reveals Independent Recruitment of Genes in the Asteraceae
Článek A Splice Site Variant in the Bovine Gene Compromises Growth and Regulation of the Inflammatory Response
Článek Promoter Nucleosome Organization Shapes the Evolution of Gene Expression
Článek The Nucleoside Diphosphate Kinase Gene Acts as Quantitative Trait Locus Promoting Non-Mendelian Inheritance
Článek The Ciliogenic Transcription Factor RFX3 Regulates Early Midline Distribution of Guidepost Neurons Required for Corpus Callosum Development
Článek Phosphorylation of the RNA–Binding Protein HOW by MAPK/ERK Enhances Its Dimerization and Activity
Článek A Genome-Wide Scan of Ashkenazi Jewish Crohn's Disease Suggests Novel Susceptibility Loci
Článek Parkinson's Disease–Associated Kinase PINK1 Regulates Miro Protein Level and Axonal Transport of Mitochondria
Článek LMW-E/CDK2 Deregulates Acinar Morphogenesis, Induces Tumorigenesis, and Associates with the Activated b-Raf-ERK1/2-mTOR Pathway in Breast Cancer Patients
Článek Mapping the Hsp90 Genetic Interaction Network in Reveals Environmental Contingency and Rewired Circuitry
Článek Autoregulation of the Noncoding RNA Gene
Článek The Human Pancreatic Islet Transcriptome: Expression of Candidate Genes for Type 1 Diabetes and the Impact of Pro-Inflammatory Cytokines
Článek Spo0A∼P Imposes a Temporal Gate for the Bimodal Expression of Competence in
Článek Antagonistic Regulation of Apoptosis and Differentiation by the Cut Transcription Factor Represents a Tumor-Suppressing Mechanism in
Článek A Downstream CpG Island Controls Transcript Initiation and Elongation and the Methylation State of the Imprinted Macro ncRNA Promoter
Článok vyšiel v časopise

PLOS Genetics

2012 Číslo 3
Najčítanejšie tento týždeň
Najčítanejšie v tomto čísle
Kurzy

Zvýšte si kvalifikáciu online z pohodlia domova

Získaná hemofilie - Povědomí o nemoci a její diagnostika
nový kurz
Eozinofilní granulomatóza s polyangiitidou
Autori: doc. MUDr. Martina Doubková, Ph.D.
Všetky kurzy
Prihlásenie
Zabudnuté heslo

Zadajte e-mailovú adresu, s ktorou ste vytvárali účet. Budú Vám na ňu zasielané informácie k nastaveniu nového hesla.

Prihlásenie

Nemáte účet?  Registrujte sa

#ADS_BOTTOM_SCRIPTS#