Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's Disease
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...
| Main Authors: | , , , , , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
Frontiers Media S.A.
2018-12-01
|
| Series: | Frontiers in Neuroscience |
| Subjects: | |
| Online Access: | https://www.frontiersin.org/article/10.3389/fnins.2018.00946/full |
| _version_ | 1819056163741761536 |
|---|---|
| author | Qiu Han Qiu Han Yong-An Sun Yong-An Sun Yu Zong Chun Chen Chun Chen Hui-Fu Wang Lan Tan Alzheimer's Disease Neuroimaging Initiative |
| author_facet | Qiu Han Qiu Han Yong-An Sun Yong-An Sun Yu Zong Chun Chen Chun Chen Hui-Fu Wang Lan Tan Alzheimer's Disease Neuroimaging Initiative |
| author_sort | Qiu Han |
| collection | DOAJ |
| description | 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-β (Aβ) 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) (Aβ1−42, 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 Aβ1−42 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 Aβ1−42 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 Aβ deposition. |
| first_indexed | 2024-12-21T13:19:03Z |
| format | Article |
| id | doaj.art-35ea10ab3a574fe0b27d264189202391 |
| institution | Directory Open Access Journal |
| issn | 1662-453X |
| language | English |
| last_indexed | 2024-12-21T13:19:03Z |
| publishDate | 2018-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Neuroscience |
| spelling | doaj.art-35ea10ab3a574fe0b27d2641892023912022-12-21T19:02:38ZengFrontiers Media S.A.Frontiers in Neuroscience1662-453X2018-12-011210.3389/fnins.2018.00946423523Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's DiseaseQiu Han0Qiu Han1Yong-An Sun2Yong-An Sun3Yu Zong4Chun Chen5Chun Chen6Hui-Fu Wang7Lan Tan8Alzheimer's Disease Neuroimaging InitiativeDepartment of Neurology, Qingdao Clinical Medical School, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, ChinaDepartment of Neurology, The Affiliated Huaian Hosipital of Xuzhou Medical University, Huai'an, ChinaDepartment of Neurology, Qingdao Clinical Medical School, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, ChinaDepartment of Neurology, First Affiliated Hospital of Kangda School, Nanjing Medical University, Lianyungang, ChinaDepartment of Neurology, School of Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, ChinaDepartment of Neurology, Qingdao Clinical Medical School, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, ChinaDepartment of Neurology, Hongze Huai'an District People's Hospital, Huai'an, ChinaDepartment of Neurology, School of Medicine, Qingdao Municipal Hospital, Qingdao University, Qingdao, ChinaDepartment of Neurology, Qingdao Clinical Medical School, Qingdao Municipal Hospital, Nanjing Medical University, Qingdao, ChinaThe 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-β (Aβ) 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) (Aβ1−42, 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 Aβ1−42 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 Aβ1−42 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 Aβ deposition.https://www.frontiersin.org/article/10.3389/fnins.2018.00946/fullPlexin-A 4 (PLXNA4)variantAlzheimer's disease (AD)amyloid-β (Aβ)association |
| spellingShingle | Qiu Han Qiu Han Yong-An Sun Yong-An Sun Yu Zong Chun Chen Chun Chen Hui-Fu Wang Lan Tan Alzheimer's Disease Neuroimaging Initiative Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's Disease Frontiers in Neuroscience Plexin-A 4 (PLXNA4) variant Alzheimer's disease (AD) amyloid-β (Aβ) association |
| title | Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's Disease |
| title_full | Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's Disease |
| title_fullStr | Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's Disease |
| title_full_unstemmed | Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's Disease |
| title_short | Common Variants in PLXNA4 and Correlation to CSF-related Phenotypes in Alzheimer's Disease |
| title_sort | common variants in plxna4 and correlation to csf related phenotypes in alzheimer s disease |
| topic | Plexin-A 4 (PLXNA4) variant Alzheimer's disease (AD) amyloid-β (Aβ) association |
| url | https://www.frontiersin.org/article/10.3389/fnins.2018.00946/full |
| work_keys_str_mv | AT qiuhan commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT qiuhan commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT yongansun commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT yongansun commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT yuzong commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT chunchen commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT chunchen commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT huifuwang commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT lantan commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease AT alzheimersdiseaseneuroimaginginitiative commonvariantsinplxna4andcorrelationtocsfrelatedphenotypesinalzheimersdisease |