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Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

Drange, Ole Kristian ; Smeland, Olav Bjerkehagen ; Shadrin, Alexey A ; Finseth, Per Ivar ; Witoelar, Aree ; Frei, Oleksandr ; Wang, Yunpeng ; Hassani, Sahar ; Djurovic, Srdjan ; Dale, Anders M ; Andreassen, Ole A

Frontiers in neuroscience, 2019-03, Vol.13, p.220-220 [Periódico revisado por pares]

Switzerland: Frontiers Research Foundation

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Título:
Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes
Autor: Drange, Ole Kristian ; Smeland, Olav Bjerkehagen ; Shadrin, Alexey A ; Finseth, Per Ivar ; Witoelar, Aree ; Frei, Oleksandr ; Wang, Yunpeng ; Hassani, Sahar ; Djurovic, Srdjan ; Dale, Anders M ; Andreassen, Ole A
Assuntos: affective symptoms ; Alzheimer's disease ; Bipolar disorder ; Cognitive ability ; cognitive symptoms ; Consortia ; Dementia ; Disease ; Epidemiology ; Genetic variance ; Genetics ; Genomes ; Genomics ; GWAS ; Hospitals ; Medicin och hälsovetenskap ; Mental disorders ; Mental health ; Neurodegenerative diseases ; Neuroscience ; pleiotropy ; Polygenic inheritance ; Protein-serine/threonine kinase ; Psychiatry ; Psychosis ; Psychotropic drugs ; R&D ; Research & development ; Schizophrenia ; Single-nucleotide polymorphism ; Studies ; Working groups
É parte de: Frontiers in neuroscience, 2019-03, Vol.13, p.220-220
Notas: ObjectType-Article-1
SourceType-Scholarly Journals-1
ObjectType-Feature-2
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Edited by: Efthimios M. C. Skoulakis, Alexander Fleming Biomedical Sciences Research Center, Greece
This article was submitted to Neurodegeneration, a section of the journal Frontiers in Neuroscience
Reviewed by: Petr A. Slominsky, Institute of Molecular Genetics (RAS), Russia; Ioannis Sotiropoulos, University of Minho, Portugal
Descrição: Alzheimer's disease (AD) and bipolar disorder (BIP) are complex traits influenced by numerous common genetic variants, most of which remain to be detected. Clinical and epidemiological evidence suggest that AD and BIP are related. However, it is not established if this relation is of genetic origin. Here, we applied statistical methods based on the conditional false discovery rate (FDR) framework to detect genetic overlap between AD and BIP and utilized this overlap to increase the power to identify common genetic variants associated with either or both traits. We obtained genome wide association studies data from the International Genomics of Alzheimer's Project part 1 (17,008 AD cases and 37,154 controls) and the Psychiatric Genetic Consortium Bipolar Disorder Working Group (20,352 BIP cases and 31,358 controls). We used conditional QQ-plots to assess overlap in common genetic variants between AD and BIP. We exploited the genetic overlap to re-rank test-statistics for AD and BIP and improve detection of genetic variants using the conditional FDR framework. Conditional QQ-plots demonstrated a polygenic overlap between AD and BIP. Using conditional FDR, we identified one novel genomic locus associated with AD, and nine novel loci associated with BIP. Further, we identified two novel loci jointly associated with AD and BIP implicating the gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect). We found polygenic overlap between AD and BIP and identified novel loci for each trait and two jointly associated loci. Further studies should examine if the shared loci implicating the and genes could explain parts of the shared and distinct features of AD and BIP.
Editor: Switzerland: Frontiers Research Foundation
Idioma: Inglês;Norueguês

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Genetic Overlap Between Alzheimer's Disease and Bipolar Disorder Implicates the MARK2 and VAC14 Genes

Drange, Ole Kristian ; Smeland, Olav Bjerkehagen ; Shadrin, Alexey A ; Finseth, Per Ivar ; Witoelar, Aree ; Frei, Oleksandr ; Wang, Yunpeng ; Hassani, Sahar ; Djurovic, Srdjan ; Dale, Anders M ; Andreassen, Ole A

Switzerland: Frontiers Research Foundation

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