| Title: |
Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration |
| Authors: |
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 |
| Publisher Information: |
Nature Research |
| Publication Year: |
2024 |
| Collection: |
Oxford University Research Archive (ORA) |
| Description: |
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. |
| Document Type: |
article in journal/newspaper |
| Language: |
English |
| DOI: |
10.1038/s42003-024-06804-3 |
| Availability: |
https://doi.org/10.1038/s42003-024-06804-3; https://ora.ox.ac.uk/objects/uuid:66d74154-5c73-4317-b92c-924dc0b1e231 |
| Rights: |
info:eu-repo/semantics/openAccess ; CC Attribution-NonCommercial-NoDerivatives (CC BY-NC-ND) |
| Accession Number: |
edsbas.1B212AA4 |
| Database: |
BASE |