Genome-wide analysis reveals genetic overlap between alcohol use behaviours, schizophrenia and bipolar disorder and identifies novel shared risk loci. Wiström, E. D., O'Connell, K. S., Karadag, N., Bahrami, S., Hindley, G. F. L., Lin, A., Cheng, W., Steen, N. E., Shadrin, A., Frei, O., Djurovic, S., Dale, A. M., Andreassen, O. A., & Smeland, O. B. Addiction, 117(3):600–610, 2022. _eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/add.15680
Genome-wide analysis reveals genetic overlap between alcohol use behaviours, schizophrenia and bipolar disorder and identifies novel shared risk loci [link]Paper  doi  abstract   bibtex   
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 \textless0.05. 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 \textless0.05. 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.
@article{wistrom_genome-wide_2022,
	title = {Genome-wide analysis reveals genetic overlap between alcohol use behaviours, schizophrenia and bipolar disorder and identifies novel shared risk loci},
	volume = {117},
	issn = {1360-0443},
	url = {https://onlinelibrary.wiley.com/doi/abs/10.1111/add.15680},
	doi = {10.1111/add.15680},
	abstract = {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 {\textless}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 {\textless}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.},
	language = {en},
	number = {3},
	urldate = {2022-04-01},
	journal = {Addiction},
	author = {Wiström, Erik D. and O'Connell, Kevin S. and Karadag, Naz and Bahrami, Shahram and Hindley, Guy F. L. and Lin, Aihua and Cheng, Weiqiu and Steen, Nils Eiel and Shadrin, Alexey and Frei, Oleksandr and Djurovic, Srdjan and Dale, Anders M. and Andreassen, Ole A. and Smeland, Olav B.},
	year = {2022},
	note = {\_eprint: https://onlinelibrary.wiley.com/doi/pdf/10.1111/add.15680},
	keywords = {AUDIT-C, Alcohol consumption, GWAS, alcohol use disorder, bipolar disorder, genetic overlap, schizophrenia.},
	pages = {600--610},
}
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