Genome-wide analysis reveals extensive genetic overlap between schizophrenia, bipolar disorder, and intelligence.
Adult
Bipolar Disorder
/ genetics
Cognitive Dysfunction
/ genetics
Databases, Genetic
Female
Genetic Loci
Genetic Predisposition to Disease
/ genetics
Genome-Wide Association Study
/ methods
Humans
Intelligence
/ genetics
Male
Multifactorial Inheritance
/ genetics
Polymorphism, Single Nucleotide
/ genetics
Schizophrenia
/ genetics
Journal
Molecular psychiatry
ISSN: 1476-5578
Titre abrégé: Mol Psychiatry
Pays: England
ID NLM: 9607835
Informations de publication
Date de publication:
04 2020
04 2020
Historique:
received:
06
07
2018
accepted:
29
11
2018
revised:
18
10
2018
pubmed:
6
1
2019
medline:
18
2
2021
entrez:
6
1
2019
Statut:
ppublish
Résumé
Schizophrenia (SCZ) and bipolar disorder (BD) are severe mental disorders associated with cognitive impairment, which is considered a major determinant of functional outcome. Despite this, the etiology of the cognitive impairment is poorly understood, and no satisfactory cognitive treatments exist. Increasing evidence indicates that genetic risk for SCZ may contribute to cognitive impairment, whereas the genetic relationship between BD and cognitive function remains unclear. Here, we combined large genome-wide association study data on SCZ (n = 82,315), BD (n = 51,710), and general intelligence (n = 269,867) to investigate overlap in common genetic variants using conditional false discovery rate (condFDR) analysis. We observed substantial genetic enrichment in both SCZ and BD conditional on associations with intelligence indicating polygenic overlap. Using condFDR analysis, we leveraged this enrichment to increase statistical power and identified 75 distinct genomic loci associated with both SCZ and intelligence, and 12 loci associated with both BD and intelligence at conjunctional FDR < 0.01. Among these loci, 20 are novel for SCZ, and four are novel for BD. Most SCZ risk alleles (61 of 75, 81%) were associated with poorer cognitive performance, whereas most BD risk alleles (9 of 12, 75%) were associated with better cognitive performance. A gene set analysis of the loci shared between SCZ and intelligence implicated biological processes related to neurodevelopment, synaptic integrity, and neurotransmission; the same analysis for BD was underpowered. Altogether, the study demonstrates that both SCZ and BD share genetic influences with intelligence, albeit in a different manner, providing new insights into their genetic architectures.
Identifiants
pubmed: 30610197
doi: 10.1038/s41380-018-0332-x
pii: 10.1038/s41380-018-0332-x
pmc: PMC6609490
mid: NIHMS1021315
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
844-853Subventions
Organisme : NIDA NIH HHS
ID : U24 DA041147
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA051039
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041093
Pays : United States
Organisme : NIDA NIH HHS
ID : U24 DA041123
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041089
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041106
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041048
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041148
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041174
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA041025
Pays : United States
Organisme : NIMH NIH HHS
ID : U01 MH109536
Pays : United States
Organisme : NIDA NIH HHS
ID : U01 DA050989
Pays : United States
Commentaires et corrections
Type : ErratumIn
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