Characterising the shared genetic determinants of bipolar disorder, schizophrenia and risk-taking.
Journal
Translational psychiatry
ISSN: 2158-3188
Titre abrégé: Transl Psychiatry
Pays: United States
ID NLM: 101562664
Informations de publication
Date de publication:
08 09 2021
08 09 2021
Historique:
received:
19
02
2021
accepted:
18
08
2021
revised:
19
07
2021
entrez:
9
9
2021
pubmed:
10
9
2021
medline:
12
10
2021
Statut:
epublish
Résumé
Increased risk-taking is a central component of bipolar disorder (BIP) and is implicated in schizophrenia (SCZ). Risky behaviours, including smoking and alcohol use, are overrepresented in both disorders and associated with poor health outcomes. Positive genetic correlations are reported but an improved understanding of the shared genetic architecture between risk phenotypes and psychiatric disorders may provide insights into underlying neurobiological mechanisms. We aimed to characterise the genetic overlap between risk phenotypes and SCZ, and BIP by estimating the total number of shared variants using the bivariate causal mixture model and identifying shared genomic loci using the conjunctional false discovery rate method. Summary statistics from genome wide association studies of SCZ, BIP, risk-taking and risky behaviours were acquired (n = 82,315-466,751). Genomic loci were functionally annotated using FUMA. Of 8.6-8.7 K variants predicted to influence BIP, 6.6 K and 7.4 K were predicted to influence risk-taking and risky behaviours, respectively. Similarly, of 10.2-10.3 K variants influencing SCZ, 9.6 and 8.8 K were predicted to influence risk-taking and risky behaviours, respectively. We identified 192 loci jointly associated with SCZ and risk phenotypes and 206 associated with BIP and risk phenotypes, of which 68 were common to both risk-taking and risky behaviours and 124 were novel to SCZ or BIP. Functional annotation implicated differential expression in multiple cortical and sub-cortical regions. In conclusion, we report extensive polygenic overlap between risk phenotypes and BIP and SCZ, identify specific loci contributing to this shared risk and highlight biologically plausible mechanisms that may underlie risk-taking in severe psychiatric disorders.
Identifiants
pubmed: 34497263
doi: 10.1038/s41398-021-01576-4
pii: 10.1038/s41398-021-01576-4
pmc: PMC8426401
doi:
Types de publication
Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
466Subventions
Organisme : NIMH NIH HHS
ID : R01 MH109897
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH075916
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH103392
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH109677
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH084053
Pays : United States
Organisme : NIDA NIH HHS
ID : HHSN271201300031C
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH110921
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH066392
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH080405
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH085542
Pays : United States
Organisme : NIMH NIH HHS
ID : R37 MH057881
Pays : United States
Organisme : NIBIB NIH HHS
ID : R01 EB000790
Pays : United States
Organisme : NINDS NIH HHS
ID : R01 NS057198
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH097276
Pays : United States
Organisme : NIA NIH HHS
ID : P01 AG002219
Pays : United States
Organisme : NIMH NIH HHS
ID : R01 MH093725
Pays : United States
Organisme : NIA NIH HHS
ID : P50 AG005138
Pays : United States
Organisme : NIMH NIH HHS
ID : P50 MH096891
Pays : United States
Informations de copyright
© 2021. The Author(s).
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