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Sökning: onr:"swepub:oai:DiVA.org:uu-303900" > Trans-ethnic Fine M...

  • Mahajan, AnubhaUniv Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England (författare)

Trans-ethnic Fine Mapping Highlights Kidney-Function Genes Linked to Salt Sensitivity

  • Artikel/kapitelEngelska2016

Förlag, utgivningsår, omfång ...

  • Elsevier BV,2016
  • electronicrdacarrier

Nummerbeteckningar

  • LIBRIS-ID:oai:DiVA.org:uu-303900
  • https://urn.kb.se/resolve?urn=urn:nbn:se:uu:diva-303900URI
  • https://doi.org/10.1016/j.ajhg.2016.07.012DOI
  • https://urn.kb.se/resolve?urn=urn:nbn:se:du-23051URI

Kompletterande språkuppgifter

  • Språk:engelska
  • Sammanfattning på:engelska

Ingår i deldatabas

Klassifikation

  • Ämneskategori:ref swepub-contenttype
  • Ämneskategori:art swepub-publicationtype

Anmärkningar

  • We analyzed genome-wide association studies (GWASs), including data from 71,638 individuals from four ancestries, for estimated glomerular filtration rate (eGFR), a measure of kidney function used to define chronic kidney disease (CKD). We identified 20 loci attaining genome-wide-significant evidence of association (p < 5 × 10(-8)) with kidney function and highlighted that allelic effects on eGFR at lead SNPs are homogeneous across ancestries. We leveraged differences in the pattern of linkage disequilibrium between diverse populations to fine-map the 20 loci through construction of "credible sets" of variants driving eGFR association signals. Credible variants at the 20 eGFR loci were enriched for DNase I hypersensitivity sites (DHSs) in human kidney cells. DHS credible variants were expression quantitative trait loci for NFATC1 and RGS14 (at the SLC34A1 locus) in multiple tissues. Loss-of-function mutations in ancestral orthologs of both genes in Drosophila melanogaster were associated with altered sensitivity to salt stress. Renal mRNA expression of Nfatc1 and Rgs14 in a salt-sensitive mouse model was also reduced after exposure to a high-salt diet or induced CKD. Our study (1) demonstrates the utility of trans-ethnic fine mapping through integration of GWASs involving diverse populations with genomic annotation from relevant tissues to define molecular mechanisms by which association signals exert their effect and (2) suggests that salt sensitivity might be an important marker for biological processes that affect kidney function and CKD in humans.

Ämnesord och genrebeteckningar

Biuppslag (personer, institutioner, konferenser, titlar ...)

  • Rodan, Aylin R.Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA (författare)
  • Le, Thu H.Department of Medicine, University of Virginia, Charlottesville, VA 22908, USA (författare)
  • Gaulton, Kyle J.Department of Pediatrics, University of California San Diego, La Jolla, CA 92093, USA (författare)
  • Haessler, JeffreyDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA (författare)
  • Stilp, Adrienne M.Department of Biostatistics, University of Washington, Seattle, WA 98195, USA (författare)
  • Kamatani, YoichiroLaboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan (författare)
  • Zhu, GuGenetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia (författare)
  • Sofer, TamarDepartment of Biostatistics, University of Washington, Seattle, WA 98195, USA (författare)
  • Puri, SanjanaUniv Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA (författare)
  • Schellinger, Jeffrey N.Univ Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA (författare)
  • Chu, Pei-LunDepartment of Medicine, University of Virginia, Charlottesville, VA 22908, USA (författare)
  • Cechova, SylviaDepartment of Medicine, University of Virginia, Charlottesville, VA 22908, USA (författare)
  • van Zuydam, NatalieUniv Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England (författare)
  • Ärnlöv, JohanHögskolan Dalarna,Uppsala universitet,Kardiovaskulär epidemiologi,School of Health and Social Studies, Dalarna University, Falun 791 88, Sweden,Medicinsk vetenskap,Uppsala university(Swepub:du)jan (författare)
  • Flessner, Michael F.National Institute of Diabetes, Digestive, and Kidney Disease, NIH, Bethesda, MD 20892, USA (författare)
  • Giedraitis, VilmantasUppsala universitet,Geriatrik(Swepub:uu)vigie517 (författare)
  • Heath, Andrew C.Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA (författare)
  • Kubo, MichiakiLaboratory for Genotyping Development, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan (författare)
  • Larsson, AndersUppsala universitet,Biokemisk struktur och funktion(Swepub:uu)andla606 (författare)
  • Lindgren, Cecilia M.Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England; Big Data Institute, Li Ka Shing Centre for Health Information and Discovery, University of Oxford, Oxford OX3 7BN, UK (författare)
  • Madden, Pamela A. F.Department of Psychiatry, Washington University in St. Louis, St. Louis, MO 63110, USA (författare)
  • Montgomery, Grant W.Molecular Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia (författare)
  • Papanicolaou, George J.Epidemiology Branch, Division of Cardiovascular Sciences, National Heart, Lung and Blood Institute, Bethesda, MD 20892, USA (författare)
  • Reiner, Alex P.Division of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA (författare)
  • Sundström, JohanUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)johasund (författare)
  • Thornton, Timothy A.Department of Biostatistics, University of Washington, Seattle, WA 98195, USA (författare)
  • Lind, LarsUppsala universitet,Kardiovaskulär epidemiologi(Swepub:uu)larslind (författare)
  • Ingelsson, ErikUppsala universitet,Molekylär epidemiologi,Science for Life Laboratory, SciLifeLab,Department of Medicine, Division of Cardiovascular Medicine, Stanford University School of Medicine, Stanford, CA 94305, USA(Swepub:uu)ering425 (författare)
  • Cai, JianwenCollaborative Studies Coordinating Center, Department of Biostatistics, University of North Carolina at Chapel Hill, Chapel Hill, NC 27599, USA (författare)
  • Martin, Nicholas G.Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia (författare)
  • Kooperberg, CharlesDivision of Public Health Sciences, Fred Hutchinson Cancer Research Center, Seattle, WA 98109, USA (författare)
  • Matsuda, KoichiLaboratory of Molecular Medicine, Human Genome Center, Institute of Medical Science, University of Tokyo, Tokyo 108-8639, Japan (författare)
  • Whitfield, John B.Genetic Epidemiology Laboratory, QIMR Berghofer Medical Research Institute, Brisbane 4006, Australia (författare)
  • Okada, YukinoriLaboratory for Statistical Analysis, RIKEN Center for Integrative Medical Sciences, Yokohama 230-0045, Japan; Department of Statistical Genetics, Osaka University Graduate School of Medicine, Osaka 565-0871, Japan (författare)
  • Laurie, Cathy C.Department of Biostatistics, University of Washington, Seattle, WA 98195, USA (författare)
  • Morris, Andrew P.Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, England; Department of Biostatistics, University of Liverpool, Liverpool L69 3GL, UK (författare)
  • Franceschini, NoraDepartment of Epidemiology, University of North Carolina, Chapel Hill, NC 27514, USA (författare)
  • Univ Oxford, Wellcome Trust Ctr Human Genet, Oxford OX3 7BN, EnglandUniv Texas Southwestern Med Ctr Dallas, Dept Internal Med, Dallas, TX 75229 USA (creator_code:org_t)

Sammanhörande titlar

  • Ingår i:American Journal of Human Genetics: Elsevier BV99:3, s. 636-6460002-92971537-6605

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