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P2‐436: GWAS IDENTIFIES CD1A AFFECTING THE RATE OF PLASMA NEUROFILAMENT LIGHT INCREASE IN NONDEMENTED ELDERS
Author(s) -
Wang Zuo-teng,
Yu Jin-Tai
Publication year - 2019
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2019.06.2843
Subject(s) - genome wide association study , minor allele frequency , proportional hazards model , medicine , single nucleotide polymorphism , oncology , neurodegeneration , linkage disequilibrium , endophenotype , disease , allele , biology , genetics , genotype , gene , psychiatry , cognition
Background: The plasma neurofilament light (NFL) levels reflect the preclinical neurodegeneration in Alzheimer’s disease (AD). In a genome-wide association study (GWAS), baseline plasma NFL data were used as endophenotypes to explore genetic factors and identified a new AD risk locus. Since inter-individual variability may exist in the disease trajectories, we performed a GWAS using a quantitative measure of the rate of change in plasma NFL levels. Methods: Five hundred forty-five qualified non-Hispanic white participants from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) with longitudinal plasma NFL data were included. Linear mixedmodels were utilized to compute longitudinal rates of change in the plasma NFL levels. Additive genetic model was utilized to explore associations between the rate of change in plasma NFL and genetic polymorphisms. Linear mixed models were used to estimate associations between genotypes and other AD-related phenotypes. Kaplan-Meier survival and Cox regression analyses were utilized to explore the impact of genetic variant on clinical disease progression. Results: Three SNPs (rs16840041, p1⁄44.50310; rs2269714, p1⁄44.50310; rs2269715, p1⁄44.83310) in CD1A were significantly associated with the rate of change in plasma NFL. The three SNPs were in linkage disequilibrium (LD). The minor allele (A) of rs16840041 was significantly associated with faster rates of [F]-Fluorodeoxyglucose (FDG) decline (estimate -1.6% per year [95% CI -0.6 to -2.6], p1⁄40.0024). Subjects with minor allele (A) showed significantly shorter estimated time of clinical disease progression (4.86 6 0.50 years, 95% CI 3.90–5.82, p 1⁄4 0.006). Conclusions: GWAS identified three SNPs (rs16840041, rs2269714 and rs2269715) within CD1Awere associated with the rate of plasma NFL increase in non-demented elders. Our results may provide new insights into the diagnostic and therapeutic methods of neurodegenerative diseases such as AD.