Communications biology · 2024
Genome-wide association study meta-analysis of neurofilament light (NfL) levels in blood reveals novel loci related to neurodegeneration.
СтатьяМетаанализПоддержка NIH: внешняя программаНазвание и аннотация: Перевод в очереди
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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
Аннотация
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.