Cristin-resultat-ID: 1684595
Sist endret: 26. mars 2020, 11:13
NVI-rapporteringsår: 2019
Resultat
Vitenskapelig artikkel
2019

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

Bidragsytere:
  • Ole Kristian Drange
  • Olav Bjerkehagen Smeland
  • Alexey A. Shadrin
  • Per Ivar Finseth
  • Aree Witoelar
  • Oleksandr Frei
  • mfl.

Tidsskrift

Frontiers in Neuroscience
ISSN 1662-4548
e-ISSN 1662-453X
NVI-nivå 1

Om resultatet

Vitenskapelig artikkel
Publiseringsår: 2019
Volum: 13
Artikkelnummer: 220
Open Access

Importkilder

Scopus-ID: 2-s2.0-85072724692

Beskrivelse Beskrivelse

Tittel

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

Sammendrag

Background: 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. Methods: 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. Results: 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 MARK2 gene (lead SNP rs10792421, conjunctional FDR = 0.030, same direction of effect) and the VAC14 gene (lead SNP rs11649476, conjunctional FDR = 0.022, opposite direction of effect). Conclusion: 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 MARK2 and VAC14 genes could explain parts of the shared and distinct features of AD and BIP.

Bidragsytere

Ole Kristian Drange

  • Tilknyttet:
    Forfatter
    ved Institutt for psykisk helse ved Norges teknisk-naturvitenskapelige universitet
  • Tilknyttet:
    Forfatter
    ved PH - Avd. for psykiatrisk akutt og mottaksfunksjon ved St. Olavs Hospital HF

Olav Bjerkehagen Smeland

  • Tilknyttet:
    Forfatter
    ved Senter for presisjonspsykiatri ved Universitetet i Oslo
  • Tilknyttet:
    Forfatter
    ved Psykoseforskning, seksjon (NORMENT/KG Jebsen OUS) ved Oslo universitetssykehus HF

Alexey Shadrin

Bidragsyterens navn vises på dette resultatet som Alexey A. Shadrin
  • Tilknyttet:
    Forfatter
    ved Senter for presisjonspsykiatri ved Universitetet i Oslo

Per Ivar Finseth

  • Tilknyttet:
    Forfatter
    ved PH - Avd. for sikkerhets-, fengsels- og rettspsykiatri ved St. Olavs Hospital HF

Aree Widya Witoelar

Bidragsyterens navn vises på dette resultatet som Aree Witoelar
  • Tilknyttet:
    Forfatter
    ved Psykoseforskning, seksjon (NORMENT/KG Jebsen OUS) ved Oslo universitetssykehus HF
  • Tilknyttet:
    Forfatter
    ved Senter for presisjonspsykiatri ved Universitetet i Oslo
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