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

作者：Zhong, Xiao-ling; Li, Jie-Qiong; Sun, Li; Li, Ya-Qing; Wang, Hui-Fu; Cao, Xi-Peng; Tan, Chen-Chen; Wang, Ling; Tan, Lan^*; Yu, Jin-Tai^*

来源：Neurotoxicity Research, 2019, 35(1): 41-48.

DOI：10.1007/s12640-018-9922-2

• -Synuclein
• Cerebrospinal fluid
• Endophenotype
• Genome-wide association studies

-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 -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 -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 -synuclein levels at genome-wide significance (P=4.167x10(-9) and 9.56x10(-9), respectively). In addition, single nucleotide polymorphisms (SNPs) near amyloid beta precursor protein (APP) (rs1394839) (P=2.31x10(-7)), Rap guanine nucleotide exchange factor 1 (RAPGEF1) (rs10901091) (P=8.07x10(-7)), and two intergenic loci on chromosome 2 and 14 (rs11687064 P=2.50x10(-7)and rs7147386 P=4.05x10(-7)) were identified as suggestive loci associated with CSF -synuclein levels. We have identified significantly associated SNPs for CSF -synuclein. These associations have important implications for a better understanding of -synuclein regulation and allow researchers to further explore the relationships between these SNPs and -synuclein-related neurodegenerative disorders.

• 出版日期2019-1
• 单位青岛市市立医院; 武汉大学; 青岛大学