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Neurotox Res. 2019 Jan;35(1):41-48. doi: 10.1007/s12640-018-9922-2. Epub 2018 Jun 29.

A Genome-Wide Association Study of α-Synuclein Levels in Cerebrospinal Fluid.

Author information

1
Department of Neurology, Qingdao Central Hospital, Qingdao University, No.127 Siliu South Road, Qingdao, 266042, Shandong Province, China.
2
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
3
Department of Neurology, Zhongnan Hospital, Wuhan University, Wuhan, China.
4
Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, China.
5
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. dr.tanlan@163.com.
6
Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. dr.tanlan@163.com.
7
Department of Neurology, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. yu-jintai@163.com.
8
Clinical Research Center, Qingdao Municipal Hospital, Qingdao University, Qingdao, China. yu-jintai@163.com.
9
Department of Neurology, University of California, San Francisco, 675 Nelson Rising Lane, Suite 190, Box 1207, San Francisco, CA, 94158, USA. yu-jintai@163.com.

Abstract

α-Synuclein is a 140-amino acid protein produced predominantly by neurons in the brain which plays a role in the regulation of neurotransmitter release, synaptic function, and plasticity, thus making it the focus in understanding the etiology of a group of neurodegenerative diseases. We conducted genome-wide association studies (GWAS) of α-synuclein levels in cerebrospinal fluid (CSF) with 209 non-Hispanic white participants from the Alzheimer's Disease Neuroimaging Initiative (ADNI-1) cohort using a linear regression model to identify novel variants associated with α-synuclein concentration. The minor allele (T) of rs7072338 in the long intergenic non-protein coding RNA 1515 (LINC01515) and the minor allele (T) of rs17794023 in clusterin-associated protein 1 (CLUAP1) were associated with higher CSF α-synuclein levels at genome-wide significance (P = 4.167 × 10-9 and 9.56 × 10-9, respectively). In addition, single nucleotide polymorphisms (SNPs) near amyloid beta precursor protein (APP) (rs1394839) (P = 2.31 × 10-7), Rap guanine nucleotide exchange factor 1 (RAPGEF1) (rs10901091) (P = 8.07 × 10-7), and two intergenic loci on chromosome 2 and 14 (rs11687064 P = 2.50 × 10-7and rs7147386 P = 4.05 × 10-7) were identified as suggestive loci associated with CSF α-synuclein levels. We have identified significantly associated SNPs for CSF α-synuclein. These associations have important implications for a better understanding of α-synuclein regulation and allow researchers to further explore the relationships between these SNPs and α-synuclein-related neurodegenerative disorders.

KEYWORDS:

Cerebrospinal fluid; Endophenotype; Genome-wide association studies; α-Synuclein

PMID:
29959729
DOI:
10.1007/s12640-018-9922-2
[Indexed for MEDLINE]

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