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Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's Disease.


ABSTRACT: The Plexin-A 4 (PLXNA4) gene, has recently been identified in genome wide association studies (GWAS), as a novel genetic player associated with Alzheimer's disease (AD). Additionally, PLXNA4 genetic variations were also found to increase AD risk by tau pathology in vitro. However, the potential roles of PLXNA4 variants in the amyloid-? (A?) pathology, were not evaluated. Five targeted loci capturing the top common variations in PLXNA4, were extracted using tagger methods. Multiple linear regression models were used to explore whether these variations can affect the cerebrospinal fluid (CSF) (A?1-42, T-tau, and P-tau) phenotypes in the Alzheimer's disease Neuroimaging Initiative (ADNI) dataset. We detected that two loci (rs6467431, rs67468325) were significantly associated with CSF A?1-42 levels in the hybrid population (rs6467431: P = 0.01376, rs67468325: P = 0.006536) and the significance remained after false discovery rate (FDR) correction (rs6467431: Pc = 0.03441, rs67468325: Pc = 0.03268). In the subgroup analysis, we further confirmed the association of rs6467431 in the cognitively normal (CN) subgroup (P = 0.01904, Pc = 0.04761). Furthermore, rs6467431-A carriers and rs67468325-G carriers showed higher CSF A?1-42 levels than non-carriers. Nevertheless, we did not detect any significant relationships between the levels of T-tau, P-tau and these PLXNA4 loci. Our findings provided preliminary evidence that PLXNA4 variants can confer AD risk through modulating the A? deposition.

SUBMITTER: Han Q 

PROVIDER: S-EPMC6305543 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Common Variants in <i>PLXNA4</i> and Correlation to CSF-related Phenotypes in Alzheimer's Disease.

Han Qiu Q   Sun Yong-An YA   Zong Yu Y   Chen Chun C   Wang Hui-Fu HF   Tan Lan L  

Frontiers in neuroscience 20181218


The Plexin-A 4 (<i>PLXNA4</i>) gene, has recently been identified in genome wide association studies (GWAS), as a novel genetic player associated with Alzheimer's disease (AD). Additionally, <i>PLXNA4</i> genetic variations were also found to increase AD risk by tau pathology <i>in vitro</i>. However, the potential roles of <i>PLXNA4</i> variants in the amyloid-β (Aβ) pathology, were not evaluated. Five targeted loci capturing the top common variations in <i>PLXNA4</i>, were extracted using tagg  ...[more]

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