Research Paper Volume 11, Issue 13 pp 4521—4535
Genome-wide association study identifies CD1A associated with rate of increase in plasma neurofilament light in non-demented elders
- 1 Department of Neurology, Qingdao Municipal Hospital, College of Medicine and Pharmaceutics, Ocean University of China, Qingdao, China
- 2 Department of Neurology and Institute of Neurology, Huashan Hospital, Shanghai Medical College, Fudan University, Shanghai, China
- 3 Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China
received: April 15, 2019 ; accepted: June 25, 2019 ; published: July 11, 2019 ;https://doi.org/10.18632/aging.102066
How to Cite
Copyright © 2019 Wang et al. This is an open-access article distributed under the terms of the Creative Commons Attribution (CC BY) 3.0 License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
As a marker of neuroaxonal injury, neurofilament light (NFL) in blood is robustly elevated in many neurodegenerative conditions. We aimed to discover single nucleotide polymorphisms (SNPs) associated with longitudinal changes in plasma NFL levels that affect the risk of developing neurodegenerative disease and clinical disease progression. 545 eligible non-Hispanic white participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with longitudinal plasma NFL data were included. Three SNPs (rs16840041, p=4.50×10-8; rs2269714, p=4.50×10-8; rs2269715, p=4.83×10-8) in CD1A were in high linkage disequilibrium (LD) and significantly associated with the increase in plasma NFL levels. We demonstrate a promoting effect of rs16840041-A on clinical disease progression (p = 0.006). Moreover, the minor allele (A) of rs16840041 was significantly associated with accelerated decline in [18F] Fluorodeoxyglucose (FDG) (estimate -1.6% per year [95% CI -0.6 to -2.6], p=0.0024). CD1A is a gene involved in longitudinal changes in plasma NFL levels and AD-related phenotypes among non-demented elders. Given the potential effects of these variants, CD1A should be further investigated as a gene of interest in neurodegenerative diseases and as a potential target for monitoring disease trajectories and treating disease.