Genome-wide analysis reveals genetic overlap between alcohol use behaviours, schizophrenia and bipolar disorder and identifies novel shared risk loci.
Alcohol consumption, alcohol use disorder, AUDIT-C, bipolar disorder, genetic overlap, GWAS, schizophrenia.
Journal
Addiction (Abingdon, England)
ISSN: 1360-0443
Titre abrégé: Addiction
Pays: England
ID NLM: 9304118
Informations de publication
Date de publication:
03 2022
03 2022
Historique:
received:
03
02
2021
accepted:
18
08
2021
pubmed:
3
9
2021
medline:
16
4
2022
entrez:
2
9
2021
Statut:
ppublish
Résumé
Schizophrenia (SCZ) and bipolar disorder (BD) have a high comorbidity of alcohol use disorder (AUD), and both comorbid AUD and excessive alcohol consumption (AC) have been linked to greater illness severity. We aimed to identify genomic loci jointly associated with SCZ, BD, AUD and AC to gain further insights into their shared genetic architecture. We analysed summary data (P values and Z scores) from genome-wide association studies (GWAS) using conjunctional false discovery rate (conjFDR) analysis, which increases power to discover shared genomic loci. We functionally characterized the identified loci using publicly available biological resources. AUD and AC data provided by the Million Veteran Program, derived from the United States Department of Veterans Affairs Healthcare System. SCZ and BD data provided by the Psychiatric Genomics Consortium, based on cohorts from countries in Europe, North America and Australia. AUD (34 658 cases, 167 346 controls), AC (n = 200 680), SCZ (31 013 cases and 38 918 controls), BD (20 352 cases and 31 358 controls). All participants were of European ancestry. Genomic loci shared between alcohol traits, SCZ and BD at conjFDR <0.05. Conditional Q-Q plots showed single-nucleotide polymorphism (SNP) enrichment for both alcohol traits across different levels of significance with SCZ and BD, and vice versa. Using conjFDR analysis we leveraged this genetic enrichment and identified several loci shared between SCZ and AUD (n = 28) and AC (n = 24), BD and AUD (n = 2) and AC (n = 8) at conjFDR <0.05. Among these loci, 24 are novel for AUD, 15 are novel for AC, three are novel for SCZ and one is novel for BD. There was a mixture of same and opposite effect directions among the shared loci. Alcohol use disorder and alcohol consumption share genomic loci with the psychiatric disorders schizophrenia and bipolar disorder with a mixed pattern of effect directions, indicating a complex genetic relationship between the phenotypes.
Sections du résumé
BACKGROUND AND AIM
Schizophrenia (SCZ) and bipolar disorder (BD) have a high comorbidity of alcohol use disorder (AUD), and both comorbid AUD and excessive alcohol consumption (AC) have been linked to greater illness severity. We aimed to identify genomic loci jointly associated with SCZ, BD, AUD and AC to gain further insights into their shared genetic architecture.
DESIGN
We analysed summary data (P values and Z scores) from genome-wide association studies (GWAS) using conjunctional false discovery rate (conjFDR) analysis, which increases power to discover shared genomic loci. We functionally characterized the identified loci using publicly available biological resources.
SETTING
AUD and AC data provided by the Million Veteran Program, derived from the United States Department of Veterans Affairs Healthcare System. SCZ and BD data provided by the Psychiatric Genomics Consortium, based on cohorts from countries in Europe, North America and Australia.
PARTICIPANTS
AUD (34 658 cases, 167 346 controls), AC (n = 200 680), SCZ (31 013 cases and 38 918 controls), BD (20 352 cases and 31 358 controls). All participants were of European ancestry.
MEASUREMENTS
Genomic loci shared between alcohol traits, SCZ and BD at conjFDR <0.05.
FINDINGS
Conditional Q-Q plots showed single-nucleotide polymorphism (SNP) enrichment for both alcohol traits across different levels of significance with SCZ and BD, and vice versa. Using conjFDR analysis we leveraged this genetic enrichment and identified several loci shared between SCZ and AUD (n = 28) and AC (n = 24), BD and AUD (n = 2) and AC (n = 8) at conjFDR <0.05. Among these loci, 24 are novel for AUD, 15 are novel for AC, three are novel for SCZ and one is novel for BD. There was a mixture of same and opposite effect directions among the shared loci.
CONCLUSIONS
Alcohol use disorder and alcohol consumption share genomic loci with the psychiatric disorders schizophrenia and bipolar disorder with a mixed pattern of effect directions, indicating a complex genetic relationship between the phenotypes.
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
600-610Subventions
Organisme : NIMH NIH HHS
ID : U24DA041123
Pays : United States
Informations de copyright
© 2021 The Authors. Addiction published by John Wiley & Sons Ltd on behalf of Society for the Study of Addiction.
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