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Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration.
Ahmad, Shahzad; Imtiaz, Mohammad Aslam; Mishra, Aniket; Wang, Ruiqi; Herrera-Rivero, Marisol; Bis, Joshua C; Fornage, Myriam; Roshchupkin, Gennady; Hofer, Edith; Logue, Mark; Longstreth, W T; Xia, Rui; Bouteloup, Vincent; Mosley, Thomas; Launer, Lenore J; Khalil, Michael; Kuhle, Jens; Rissman, Robert A; Chene, Genevieve; Dufouil, Carole; Djoussé, Luc; Lyons, Michael J; Mukamal, Kenneth J; Kremen, William S; Franz, Carol E; Schmidt, Reinhold; Debette, Stephanie; Breteler, Monique M B; Berger, Klaus; Yang, Qiong; Seshadri, Sudha; Aziz, N Ahmad; Ghanbari, Mohsen; Ikram, M Arfan.
Afiliação
  • Ahmad S; Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.
  • Imtiaz MA; Oxford-GSK Institute of Computational and Molecular Medicine (IMCM), Centre for Human Genetics, Nuffield Department of Medicine (NDM), University of Oxford, Oxford, OX3 7BN, UK.
  • Mishra A; Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1/99, 53127, Bonn, Germany.
  • Wang R; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.
  • Herrera-Rivero M; Boston University, Boston, MA, 02215, USA.
  • Bis JC; Department of Genetic Epidemiology, Institute of Human Genetics, University of Münster, Münster, Germany.
  • Fornage M; Department of Psychiatry, University of Münster, Münster, Germany.
  • Roshchupkin G; Cardiovascular Health Research Unit, Department of Medicine, University of Washington, 1730 Minor Ave #1360, Seattle, WA, 98101, USA.
  • Hofer E; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, 1825 Pressler Street Houston, Houston, 77030, TX, USA.
  • Logue M; Department of Epidemiology, Erasmus University Medical Center, PO Box 2040, 3000, CA, Rotterdam, the Netherlands.
  • Longstreth WT; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036, Graz, Austria.
  • Xia R; Institute for Medical Informatics, Statistics and Documentation, Medical University of Graz, Auenbruggerplatz 2, Fifth Floor, Graz, 8036, Austria.
  • Bouteloup V; National Center for PTSD, Behavioral Sciences Division at VA Boston Healthcare System, Boston, 150 South Huntington Avenue, Boston, MA, 02130, USA.
  • Mosley T; Department of Psychiatry and Biomedical Genetics, Boston University School of Medicine, Boston, 72 East Concord Street E200, Boston, MA, 02118, USA.
  • Launer LJ; Departments of Neurology and Epidemiology, University of Washington, Seattle, 3980 15th Ave NE Seattle, Seattle, WA, 98195, USA.
  • Khalil M; Brown Foundation Institute of Molecular Medicine, McGovern Medical School, University of Texas Health Science Center at Houston, 1825 Pressler Street Houston, Houston, 77030, TX, USA.
  • Kuhle J; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.
  • Rissman RA; MIND Center, University of Mississippi Medical Center, Jackson, 2500 North State Street, Jackson, MS, 39216, USA.
  • Chene G; Laboratory of Epidemiology and Population Science, NIA Intramural Research Program, 251 Bayview Blvd, Baltimore, MD, 21224, USA.
  • Dufouil C; Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036, Graz, Austria.
  • Djoussé L; Research Center for Clinical Neuroimmunology and Neuroscience University Hospital, Spitalstrasse 2, CH-4031, Basel, Switzerland.
  • Lyons MJ; Department of Physiology and Neuroscience, Alzheimer's Therapeutic Research Institute, Keck School of Medicine of the University of Southern California, California, USA.
  • Mukamal KJ; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.
  • Kremen WS; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.
  • Franz CE; Brigham and Women's Hospital, Harvard Medical School, Boston, 75 FRANCIS STREET, BOSTON MA 02115, MA, Boston, USA.
  • Schmidt R; Department of Psychological & Brain Sciences, Boston University, Boston, 64 Cummington Mall # 149, Boston, MA, 02215, USA.
  • Debette S; Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, 330 Brookline Avenue Boston, MA, 02215, USA.
  • Breteler MMB; Department of Psychiatry and Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Berger K; Department of Psychiatry and Center for Behavior Genetics of Aging, University of California, San Diego, La Jolla, CA, 92093, USA.
  • Yang Q; Clinical Division of Neurogeriatrics, Department of Neurology, Medical University of Graz, Auenbruggerplatz 22, 8036, Graz, Austria.
  • Seshadri S; University of Bordeaux, Inserm, Bordeaux Population Health Research Center, UMR 1219, F-33000, Bordeaux, France.
  • Aziz NA; CHU de Bordeaux, Department of Neurology, Institute for Neurodegenerative Diseases, F-33000, Bordeaux, France.
  • Ghanbari M; Population Health Sciences, German Center for Neurodegenerative Diseases (DZNE), Venusberg-Campus 1/99, 53127, Bonn, Germany.
  • Ikram MA; Institute for Medical Biometry, Informatics and Epidemiology (IMBIE), Faculty of Medicine, University of Bonn, Venusberg-Campus 1, 53127, Bonn, Germany.
Commun Biol ; 7(1): 1103, 2024 Sep 09.
Article em En | MEDLINE | ID: mdl-39251807
ABSTRACT
Neurofilament light chain (NfL) levels in circulation have been established as a sensitive biomarker of neuro-axonal damage across a range of neurodegenerative disorders. Elucidation of the genetic architecture of blood NfL levels could provide new insights into molecular mechanisms underlying neurodegenerative disorders. In this meta-analysis of genome-wide association studies (GWAS) of blood NfL levels from eleven cohorts of European ancestry, we identify two genome-wide significant loci at 16p12 (UMOD) and 17q24 (SLC39A11). We observe association of three loci at 1q43 (FMN2), 12q14, and 12q21 with blood NfL levels in the meta-analysis of African-American ancestry. In the trans-ethnic meta-analysis, we identify three additional genome-wide significant loci at 1p32 (FGGY), 6q14 (TBX18), and 4q21. In the post-GWAS analyses, we observe the association of higher NfL polygenic risk score with increased plasma levels of total-tau, Aß-40, Aß-42, and higher incidence of Alzheimer's disease in the Rotterdam Study. Furthermore, Mendelian randomization analysis results suggest that a lower kidney function could cause higher blood NfL levels. This study uncovers multiple genetic loci of blood NfL levels, highlighting the genes related to molecular mechanism of neurodegeneration.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Neurofilamentos / Doenças Neurodegenerativas / Estudo de Associação Genômica Ampla Limite: Female / Humans / Male Idioma: En Revista: Commun Biol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda
Texto completo
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Proteínas de Neurofilamentos / Doenças Neurodegenerativas / Estudo de Associação Genômica Ampla Limite: Female / Humans / Male Idioma: En Revista: Commun Biol Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Holanda