Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder

Emma C. Johnson; Manav Kapoor; Alexander S. Hatoum; Hang Zhou; Renato Polimanti; Frank R. Wendt; Raymond K. Walters; Dongbing Lai; Rachel L. Kember; Sarah Hartz; Jacquelyn L. Meyers; Roseann E. Peterson; Stephan Ripke; Tim B. Bigdeli; Ayman H. Fanous; Carlos N. Pato; Michele T. Pato; Alison M. Goate; Henry R. Kranzler; Michael C. O'Donovan; James T.R. Walters; Joel Gelernter; Howard J. Edenberg; Arpana Agrawal

doi:10.1017/S003329172100266X

Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder

Emma C. Johnson, Manav Kapoor, Alexander S. Hatoum, Hang Zhou, Renato Polimanti, Frank R. Wendt, Raymond K. Walters, Dongbing Lai, Rachel L. Kember, Sarah Hartz, Jacquelyn L. Meyers, Roseann E. Peterson, Stephan Ripke, Tim B. Bigdeli, Ayman H. Fanous, Carlos N. Pato, Michele T. Pato, Alison M. Goate, Henry R. Kranzler, Michael C. O'DonovanJames T.R. Walters, Joel Gelernter, Howard J. Edenberg, Arpana Agrawal

Research output: Contribution to journal › Article › peer-review

6 Scopus citations

Abstract

Background Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders. Methods We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific. Results We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). Conclusions Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

Original language	English (US)
Pages (from-to)	1196-1204
Number of pages	9
Journal	Psychological Medicine
Volume	53
Issue number	4
DOIs	https://doi.org/10.1017/S003329172100266X
State	Published - Mar 7 2023
Externally published	Yes

Keywords

Alcohol
genetic overlap
genome wide association study
pleiotropy
schizophrenia

ASJC Scopus subject areas

Applied Psychology
Psychiatry and Mental health

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10.1017/S003329172100266X

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Johnson, E. C., Kapoor, M., Hatoum, A. S., Zhou, H., Polimanti, R., Wendt, F. R., Walters, R. K., Lai, D., Kember, R. L., Hartz, S., Meyers, J. L., Peterson, R. E., Ripke, S., Bigdeli, T. B., Fanous, A. H., Pato, C. N., Pato, M. T., Goate, A. M., Kranzler, H. R., ... Agrawal, A. (2023). Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder. Psychological Medicine, 53(4), 1196-1204. https://doi.org/10.1017/S003329172100266X

Johnson, EC, Kapoor, M, Hatoum, AS, Zhou, H, Polimanti, R, Wendt, FR, Walters, RK, Lai, D, Kember, RL, Hartz, S, Meyers, JL, Peterson, RE, Ripke, S, Bigdeli, TB, Fanous, AH, Pato, CN, Pato, MT, Goate, AM, Kranzler, HR, O'Donovan, MC, Walters, JTR, Gelernter, J, Edenberg, HJ & Agrawal, A 2023, 'Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder', Psychological Medicine, vol. 53, no. 4, pp. 1196-1204. https://doi.org/10.1017/S003329172100266X

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title = "Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder",

abstract = "Background Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders. Methods We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific. Results We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). Conclusions Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.",

keywords = "Alcohol, genetic overlap, genome wide association study, pleiotropy, schizophrenia",

author = "Johnson, {Emma C.} and Manav Kapoor and Hatoum, {Alexander S.} and Hang Zhou and Renato Polimanti and Wendt, {Frank R.} and Walters, {Raymond K.} and Dongbing Lai and Kember, {Rachel L.} and Sarah Hartz and Meyers, {Jacquelyn L.} and Peterson, {Roseann E.} and Stephan Ripke and Bigdeli, {Tim B.} and Fanous, {Ayman H.} and Pato, {Carlos N.} and Pato, {Michele T.} and Goate, {Alison M.} and Kranzler, {Henry R.} and O'Donovan, {Michael C.} and Walters, {James T.R.} and Joel Gelernter and Edenberg, {Howard J.} and Arpana Agrawal",

note = "Publisher Copyright: {\textcopyright} The Author(s), 2021. Published by Cambridge University Press.",

year = "2023",

month = mar,

day = "7",

doi = "10.1017/S003329172100266X",

language = "English (US)",

volume = "53",

pages = "1196--1204",

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TY - JOUR

T1 - Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder

AU - Johnson, Emma C.

AU - Kapoor, Manav

AU - Hatoum, Alexander S.

AU - Zhou, Hang

AU - Polimanti, Renato

AU - Wendt, Frank R.

AU - Walters, Raymond K.

AU - Lai, Dongbing

AU - Kember, Rachel L.

AU - Hartz, Sarah

AU - Meyers, Jacquelyn L.

AU - Peterson, Roseann E.

AU - Ripke, Stephan

AU - Bigdeli, Tim B.

AU - Fanous, Ayman H.

AU - Pato, Carlos N.

AU - Pato, Michele T.

AU - Goate, Alison M.

AU - Kranzler, Henry R.

AU - O'Donovan, Michael C.

AU - Walters, James T.R.

AU - Gelernter, Joel

AU - Edenberg, Howard J.

AU - Agrawal, Arpana

PY - 2023/3/7

Y1 - 2023/3/7

N2 - Background Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders. Methods We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific. Results We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). Conclusions Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

AB - Background Alcohol use disorder (AUD) and schizophrenia (SCZ) frequently co-occur, and large-scale genome-wide association studies (GWAS) have identified significant genetic correlations between these disorders. Methods We used the largest published GWAS for AUD (total cases = 77 822) and SCZ (total cases = 46 827) to identify genetic variants that influence both disorders (with either the same or opposite direction of effect) and those that are disorder specific. Results We identified 55 independent genome-wide significant single nucleotide polymorphisms with the same direction of effect on AUD and SCZ, 8 with robust effects in opposite directions, and 98 with disorder-specific effects. We also found evidence for 12 genes whose pleiotropic associations with AUD and SCZ are consistent with mediation via gene expression in the prefrontal cortex. The genetic covariance between AUD and SCZ was concentrated in genomic regions functional in brain tissues (p = 0.001). Conclusions Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD.

KW - Alcohol

KW - genetic overlap

KW - genome wide association study

KW - pleiotropy

KW - schizophrenia

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SP - 1196

EP - 1204

JO - Psychological Medicine

JF - Psychological Medicine

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ER -

Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder

Abstract

Keywords

ASJC Scopus subject areas

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