APOE and MS4A6A interact with GnRH signaling in Alzheimer's disease: Enrichment of epistatic effects

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• dc.contributor.author Cáceres, Alejandro
• dc.contributor.author Vargas, José E.
• dc.contributor.author González, Juan Ramón
• dc.date.accessioned 2023-10-27T06:33:05Z
• dc.date.available 2023-10-27T06:33:05Z
• dc.date.issued 2017
• dc.description.abstract Introduction: It is unknown if risk loci, identified by genome-wide association studies of late-onset Alzheimer's disease (LOAD), are linked to common molecular mechanisms through epistatic effects. Methods: We performed genome-wide interaction studies of five risk variants for LOAD followed by enrichment analyses to find if there are pathways that simultaneously interact with more than one variant. This novel approach was applied to four independent cohorts (5393 cases and 3746 controls). Results: We found enrichment of epistasis in gonadotropin-releasing hormone signaling with risk single-nucleotide polymorphisms in APOE and MS4A6A (P value = 3.7 × 10-5, P value = 5.6 × 10-6); vascular smooth muscle contraction pathway was also enriched in epistasis with these loci (P value = 9.6 × 10-5, P value = 2.4 × 10-7). MS4A6A risk variant also interacted with dilated cardiomyopathy pathway (P value = 3.1 × 10-7). Discussion: In addition to APOE, MS4A6A polymorphisms should be considered in hormone trials targeting gonadotropins. Interactions of risk variants with neurovascular pathways may also be important in LOAD pathology.
• dc.format.mimetype application/pdf
• dc.identifier.citation Cáceres A, Vargas JE, González JR. APOE and MS4A6A interact with GnRH signaling in Alzheimer's disease: Enrichment of epistatic effects. Alzheimers Dement. 2017 Apr;13(4):493-7. DOI: 10.1016/j.jalz.2016.05.009
• dc.identifier.doi http://dx.doi.org/10.1016/j.jalz.2016.05.009
• dc.identifier.issn 1552-5260
• dc.identifier.uri http://hdl.handle.net/10230/58138
• dc.language.iso eng
• dc.publisher Wiley
• dc.relation.ispartof Alzheimers Dement. 2017 Apr;13(4):493-7
• dc.rights This is the peer reviewed version of the following article: Cáceres A, Vargas JE, González JR. APOE and MS4A6A interact with GnRH signaling in Alzheimer's disease: Enrichment of epistatic effects. Alzheimers Dement. 2017 Apr;13(4):493-7. DOI: 10.1016/j.jalz.2016.05.009, which has been published in final form at http://dx.doi.org/10.1016/j.jalz.2016.05.009. This article may be used for non-commercial purposes in accordance with Wiley Terms and Conditions for Use of Self-Archived Versions.
• dc.rights.accessRights info:eu-repo/semantics/openAccess
• dc.subject.keyword APOE
• dc.subject.keyword Alzheimer's disease
• dc.subject.keyword Epistasis
• dc.subject.keyword GWAS
• dc.subject.keyword GnRH signaling
• dc.subject.keyword Gonadotropin
• dc.subject.keyword MS4A6A
• dc.subject.keyword PICALM
• dc.subject.keyword Pathway analysis
• dc.subject.keyword SNP
• dc.title APOE and MS4A6A interact with GnRH signaling in Alzheimer's disease: Enrichment of epistatic effects
• dc.type info:eu-repo/semantics/article
• dc.type.version info:eu-repo/semantics/acceptedVersion