| Autor: |
Shahzad Ahmad, Mohammad Aslam Imtiaz, Aniket Mishra, Ruiqi Wang, Marisol Herrera-Rivero, Joshua C. Bis, Myriam Fornage, Gennady Roshchupkin, Edith Hofer, Mark Logue, W. T. Longstreth, Rui Xia, Vincent Bouteloup, Thomas Mosley, Lenore J. Launer, Michael Khalil, Jens Kuhle, Robert A. Rissman, Genevieve Chene, Carole Dufouil, Luc Djoussé, Michael J. Lyons, Kenneth J. Mukamal, William S. Kremen, Carol E. Franz, Reinhold Schmidt, Stephanie Debette, Monique M. B. Breteler, Klaus Berger, Qiong Yang, Sudha Seshadri, N. Ahmad Aziz, Mohsen Ghanbari, M. Arfan Ikram |
| Jazyk: |
angličtina |
| Rok vydání: |
2024 |
| Předmět: |
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| Zdroj: |
Communications Biology, Vol 7, Iss 1, Pp 1-12 (2024) |
| Druh dokumentu: |
article |
| ISSN: |
2399-3642 |
| DOI: |
10.1038/s42003-024-06804-3 |
| Popis: |
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. |
| Databáze: |
Directory of Open Access Journals |
| Externí odkaz: |
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