Objective: To investigate genetic contributions to the Alzheimer’s disease (AD) related cerebrospinal fluid (CSF) biomarkers in the patients with Parkinson’s disease (PD).

Background: Aβ, t-tau and p-tau are established biomarkers for Alzheimer’s disease. These biomarkers have been reported to be altered in the patients with Parkinson’s disease when compared with controls. However, its mechanism is not well-understood.

Method: We conducted genome-wide association studies (GWAS) for the CSF biomarkers using PD cohorts (Parkinson’s Progression Marker Initiative and BioFIND) as well as an AD cohort (Alzheimer’s Disease Imaging Initiative), We compare the results of the GWAS among disease status to identify the heterogeneity of genetic contributions if any. We meta-analyzed the GWAS results across  disease status when appropriate, and further combined the results from the largest CSF biomarker GWAS conducted in the AD field (Deming et al, 2017)

Results: In the meta-analysis, we had 2 loci with genome-wide signals  – APOE locus (top hit: rs429358, APOE e4 tagging SNP) for CSF Aβ and intergenic region at 3q28 between GEMC1 and OSTN (top hit: rs13065568) for CSF pTau and tTau. Both of these were reported by Deming et al. These variants don’t show evidence that the magnitude of associations are different by disease status. The other loci reported previously– 6q25 for Ab,  9q24, 13q21.1 and 18q23 for pTau were not carrying any signals in our dataset although the magnitude of effect in 18q23 loci (top hit: rs12961169) was heterogeneous and may be relevant to AD cases only. When combined with Deming et al’s GWAS results, we further identified the novel locus at 7p22 (top hit: rs60871478, an intron variant for DNAAF5) which was colocalized with the Brain expression for DNAAF5.

Conclusion: We identified three signals associated with the AD biomarkers across diseases including one novel locus at DNAAF5 .In contrast, some previously reported GWAS loci were not replicated and might be relevant to disease specific pathogenicity.

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MDS Abstracts - https://www.mdsabstracts.org/abstract/genome-wide-association-study-of-a%ce%b2-t-tau-and-p-tau-in-csf-in-parkinsons-disease/