Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
SHR Neuro Krebs Kardio Lipid Stoffw Microb
Ahmad, S; Imtiaz, MA; Mishra, A; Wang, R; Herrera-Rivero, M; Bis, JC; Fornage, M; Roshchupkin, G; Hofer, E; Logue, M; Longstreth, WT; Xia, R; Bouteloup, V; Mosley, T; Launer, LJ; Khalil, M; Kuhle, J; Rissman, RA; Chene, G; Dufouil, C; Djoussé, L; Lyons, MJ; Mukamal, KJ; Kremen, WS; Franz, CE; Schmidt, R; Debette, S; Breteler, MMB; Berger, K; Yang, Q; Seshadri, S; Aziz, NA; Ghanbari, M; Ikram, MA.
Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration.
Commun Biol. 2024; 7(1): 1103
Doi: 10.1038/s42003-024-06804-3
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- Co-Autor*innen der Med Uni Graz
- Hofer Edith
- Khalil Michael
- Schmidt Reinhold
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- 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, Aβ-40, Aβ-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.
- Find related publications in this database (using NLM MeSH Indexing)
- Humans - administration & dosage
- Genome-Wide Association Study - administration & dosage
- Neurofilament Proteins - genetics, blood
- Neurodegenerative Diseases - genetics, blood
- Genetic Predisposition to Disease - administration & dosage
- Genetic Loci - administration & dosage
- Biomarkers - blood
- Polymorphism, Single Nucleotide - administration & dosage
- Male - administration & dosage
- Female - administration & dosage
- Alzheimer Disease - genetics, blood