Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder
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.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:53 |
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| Enthalten in: |
Psychological medicine - 53(2023), 4 vom: 29. März, Seite 1196-1204 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Johnson, Emma C [VerfasserIn] |
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| Links: |
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| Themen: |
Alcohol |
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| Anmerkungen: |
Date Completed 04.04.2023 Date Revised 02.03.2024 published: Print-Electronic Citation Status MEDLINE |
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| doi: |
10.1017/S003329172100266X |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM327775335 |
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| 100 | 1 | |a Johnson, Emma C |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Investigation of convergent and divergent genetic influences underlying schizophrenia and alcohol use disorder |
| 264 | 1 | |c 2023 | |
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| 500 | |a Date Completed 04.04.2023 | ||
| 500 | |a Date Revised 02.03.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a 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 | ||
| 520 | |a 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 | ||
| 520 | |a 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) | ||
| 520 | |a CONCLUSIONS: Our findings provide further evidence that SCZ shares meaningful genetic overlap with AUD | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a Research Support, N.I.H., Extramural | |
| 650 | 4 | |a Research Support, Non-U.S. Gov't | |
| 650 | 4 | |a Alcohol | |
| 650 | 4 | |a genetic overlap | |
| 650 | 4 | |a genome wide association study | |
| 650 | 4 | |a pleiotropy | |
| 650 | 4 | |a schizophrenia | |
| 700 | 1 | |a Kapoor, Manav |e verfasserin |4 aut | |
| 700 | 1 | |a Hatoum, Alexander S |e verfasserin |4 aut | |
| 700 | 1 | |a Zhou, Hang |e verfasserin |4 aut | |
| 700 | 1 | |a Polimanti, Renato |e verfasserin |4 aut | |
| 700 | 1 | |a Wendt, Frank R |e verfasserin |4 aut | |
| 700 | 1 | |a Walters, Raymond K |e verfasserin |4 aut | |
| 700 | 1 | |a Lai, Dongbing |e verfasserin |4 aut | |
| 700 | 1 | |a Kember, Rachel L |e verfasserin |4 aut | |
| 700 | 1 | |a Hartz, Sarah |e verfasserin |4 aut | |
| 700 | 1 | |a Meyers, Jacquelyn L |e verfasserin |4 aut | |
| 700 | 1 | |a Peterson, Roseann E |e verfasserin |4 aut | |
| 700 | 1 | |a Ripke, Stephan |e verfasserin |4 aut | |
| 700 | 1 | |a Bigdeli, Tim B |e verfasserin |4 aut | |
| 700 | 1 | |a Fanous, Ayman H |e verfasserin |4 aut | |
| 700 | 1 | |a Pato, Carlos N |e verfasserin |4 aut | |
| 700 | 1 | |a Pato, Michele T |e verfasserin |4 aut | |
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| 700 | 1 | |a Edenberg, Howard J |e verfasserin |4 aut | |
| 700 | 1 | |a Agrawal, Arpana |e verfasserin |4 aut | |
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