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Sex-specific and pleiotropic effects underlying kidney function identified from GWAS meta-analysis.
Graham, Sarah E; Nielsen, Jonas B; Zawistowski, Matthew; Zhou, Wei; Fritsche, Lars G; Gabrielsen, Maiken E; Skogholt, Anne Heidi; Surakka, Ida; Hornsby, Whitney E; Fermin, Damian; Larach, Daniel B; Kheterpal, Sachin; Brummett, Chad M; Lee, Seunggeun; Kang, Hyun Min; Abecasis, Goncalo R; Romundstad, Solfrid; Hallan, Stein; Sampson, Matthew G; Hveem, Kristian; Willer, Cristen J.
Afiliação
  • Graham SE; Department of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Nielsen JB; Department of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Zawistowski M; Department of Biostatistics: Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Zhou W; Department of Computational Medicine and Bioinformatics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Fritsche LG; Department of Biostatistics: Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Gabrielsen ME; K.G. Jebsen Center for Genetic Epidemiology, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 7491, Norway.
  • Skogholt AH; Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 7491, Norway.
  • Surakka I; K.G. Jebsen Center for Genetic Epidemiology, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 7491, Norway.
  • Hornsby WE; Department of Public Health and Nursing, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 7491, Norway.
  • Fermin D; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 7491, Norway.
  • Larach DB; Department of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Kheterpal S; Department of Internal Medicine: Cardiology, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Brummett CM; Department of Pediatrics: Pediatric Nephrology, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Lee S; Department of Anesthesiology, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Kang HM; Department of Anesthesiology, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Abecasis GR; Department of Anesthesiology, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Romundstad S; Department of Biostatistics: Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Hallan S; Department of Biostatistics: Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Sampson MG; Department of Biostatistics: Center for Statistical Genetics, University of Michigan, Ann Arbor, 48109, MI, USA.
  • Hveem K; Department of Clinical and Molecular Medicine, Faculty of Medicine and Health Sciences, Norwegian University of Science and Technology, Trondheim, 7491, Norway.
  • Willer CJ; Department of Internal Medicine, Levanger Hospital, Health Trust Nord-Trøndelag, Levanger, 7600, Norway.
Nat Commun ; 10(1): 1847, 2019 04 23.
Article em En | MEDLINE | ID: mdl-31015462
ABSTRACT
Chronic kidney disease (CKD) is a growing health burden currently affecting 10-15% of adults worldwide. Estimated glomerular filtration rate (eGFR) as a marker of kidney function is commonly used to diagnose CKD. We analyze eGFR data from the Nord-Trøndelag Health Study and Michigan Genomics Initiative and perform a GWAS meta-analysis with public summary statistics, more than doubling the sample size of previous meta-analyses. We identify 147 loci (53 novel) associated with eGFR, including genes involved in transcriptional regulation, kidney development, cellular signaling, metabolism, and solute transport. Additionally, sex-stratified analysis identifies one locus with more significant effects in women than men. Using genetic risk scores constructed from these eGFR meta-analysis results, we show that associated variants are generally predictive of CKD with only modest improvements in detection compared with other known clinical risk factors. Collectively, these results yield additional insight into the genetic factors underlying kidney function and progression to CKD.
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Texto completo: 1 Base de dados: MEDLINE Assunto principal: Insuficiência Renal Crônica / Estudo de Associação Genômica Ampla / Loci Gênicos / Taxa de Filtração Glomerular Idioma: En Ano de publicação: 2019 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Base de dados: MEDLINE Assunto principal: Insuficiência Renal Crônica / Estudo de Associação Genômica Ampla / Loci Gênicos / Taxa de Filtração Glomerular Idioma: En Ano de publicação: 2019 Tipo de documento: Article