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Psychological medicine
03, 2023;53 (4): 1196-1204.

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
Author Information
  1. Emma C Johnson: Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. ORCID
  2. Manav Kapoor: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ORCID
  3. Alexander S Hatoum: Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. ORCID
  4. Hang Zhou: Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, CT, USA.
  5. Renato Polimanti: Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, CT, USA. ORCID
  6. Frank R Wendt: Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, CT, USA. ORCID
  7. Raymond K Walters: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. ORCID
  8. Dongbing Lai: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. ORCID
  9. Rachel L Kember: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. ORCID
  10. Sarah Hartz: Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. ORCID
  11. Jacquelyn L Meyers: Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA. ORCID
  12. Roseann E Peterson: Department of Psychiatry, Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA. ORCID
  13. Stephan Ripke: Analytic and Translational Genetics Unit, Department of Medicine, Massachusetts General Hospital and Harvard Medical School, Boston, MA, USA. ORCID
  14. Tim B Bigdeli: Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA. ORCID
  15. Ayman H Fanous: Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA. ORCID
  16. Carlos N Pato: Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA. ORCID
  17. Michele T Pato: Department of Psychiatry and Behavioral Sciences, SUNY Downstate Health Sciences University, Brooklyn, NY, USA. ORCID
  18. Alison M Goate: Department of Neuroscience, Icahn School of Medicine at Mount Sinai, New York, NY, USA. ORCID
  19. Henry R Kranzler: Department of Psychiatry, University of Pennsylvania Perelman School of Medicine, Philadelphia, PA, USA. ORCID
  20. Michael C O'Donovan: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK.
  21. James T R Walters: Division of Psychological Medicine and Clinical Neurosciences, MRC Centre for Neuropsychiatric Genetics and Genomics, Cardiff University School of Medicine, Cardiff, UK.
  22. Joel Gelernter: Department of Psychiatry, Division of Human Genetics, Yale University School of Medicine, New Haven, CT, USA. ORCID
  23. Howard J Edenberg: Department of Medical and Molecular Genetics, Indiana University School of Medicine, Indianapolis, IN, USA. ORCID
  24. Arpana Agrawal: Department of Psychiatry, Washington University School of Medicine, Saint Louis, MO, USA. ORCID
PMID: 34231451 DOI: 10.1017/S003329172100266X

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 ( = 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

References

Lancet. 2013 Nov 9;382(9904):1575-86 [PMID: 23993280]
PLoS Comput Biol. 2015 Apr 17;11(4):e1004219 [PMID: 25885710]
Cell. 2019 Dec 12;179(7):1469-1482.e11 [PMID: 31835028]
Nat Neurosci. 2015 Dec;18(12):1707-12 [PMID: 26605881]
Lancet Psychiatry. 2020 Dec;7(12):1032-1045 [PMID: 33096046]
Mol Psychiatry. 2020 Oct;25(10):2455-2467 [PMID: 31591465]
Nat Genet. 2019 Feb;51(2):237-244 [PMID: 30643251]
Am J Hum Genet. 2019 Aug 1;105(2):334-350 [PMID: 31374203]
Nat Genet. 2016 May;48(5):481-7 [PMID: 27019110]
Nat Commun. 2019 Apr 2;10(1):1499 [PMID: 30940813]
Neuropsychopharmacology. 2022 Sep;47(10):1739-1745 [PMID: 34750568]
PLoS Genet. 2017 Jul 24;13(7):e1006933 [PMID: 28742084]
Hosp Community Psychiatry. 1989 Oct;40(10):1041-6 [PMID: 2807205]
Nat Neurosci. 2018 Dec;21(12):1656-1669 [PMID: 30482948]
Mol Psychiatry. 2017 Oct;22(10):1376-1384 [PMID: 28937693]
Bioinformatics. 2011 Jun 15;27(12):1739-40 [PMID: 21546393]
Nat Genet. 2015 Mar;47(3):291-5 [PMID: 25642630]
Addict Biol. 2018 Jan;23(1):485-492 [PMID: 28231610]
Nat Genet. 2015 Nov;47(11):1236-41 [PMID: 26414676]
Am J Hum Genet. 2012 May 4;90(5):821-35 [PMID: 22560090]
Am J Hum Genet. 2017 Dec 7;101(6):939-964 [PMID: 29220677]
Nat Genet. 2019 Jan;51(1):63-75 [PMID: 30478444]
Am J Psychiatry. 1993 Aug;150(8):1255-6 [PMID: 8328573]
Drug Alcohol Depend. 2018 Oct 1;191:234-258 [PMID: 30153606]
Nature. 2014 Jul 24;511(7510):421-7 [PMID: 25056061]
Nat Commun. 2018 Jan 15;9(1):224 [PMID: 29335400]
Nat Genet. 2019 Sep;51(9):1339-1348 [PMID: 31427789]
Br J Psychiatry. 1994 May;164(5):630-6 [PMID: 7921713]
Nat Neurosci. 2020 Jul;23(7):809-818 [PMID: 32451486]
Nature. 2017 Oct 11;550(7675):204-213 [PMID: 29022597]
Arch Gen Psychiatry. 2003 Dec;60(12):1187-92 [PMID: 14662550]
Nature. 2014 Apr 10;508(7495):199-206 [PMID: 24695229]
Nat Genet. 2013 Jun;45(6):580-5 [PMID: 23715323]
Nat Neurosci. 2016 Nov;19(11):1442-1453 [PMID: 27668389]
Nat Commun. 2017 Nov 28;8(1):1826 [PMID: 29184056]
Bioinformatics. 2010 Sep 1;26(17):2190-1 [PMID: 20616382]
Sci Rep. 2015 May 27;5:10576 [PMID: 26015273]
Nat Genet. 2018 Mar;50(3):381-389 [PMID: 29483656]
Psychol Med. 2015 Apr;45(5):1061-72 [PMID: 25171596]
Transl Psychiatry. 2019 Feb 14;9(1):89 [PMID: 30765688]
Nat Neurosci. 2019 Mar;22(3):343-352 [PMID: 30718901]
Nat Genet. 2019 May;51(5):793-803 [PMID: 31043756]
Psychol Med. 2020 Feb;50(3):484-498 [PMID: 30874500]
Nat Hum Behav. 2021 Aug;5(8):1065-1073 [PMID: 33686200]
Am J Psychiatry. 2019 Feb 1;176(2):107-118 [PMID: 30336701]
JAMA Psychiatry. 2020 Oct 1;77(10):1072-1080 [PMID: 32492095]
PLoS Genet. 2016 Apr 08;12(4):e1005947 [PMID: 27058395]
Lancet Psychiatry. 2019 Dec;6(12):1068-1080 [PMID: 31630984]
Nat Genet. 2019 Mar;51(3):445-451 [PMID: 30643256]
Sci Data. 2018 Aug 07;5:180142 [PMID: 30084846]
Nat Genet. 2018 Apr;50(4):621-629 [PMID: 29632380]
Cell. 2018 Jun 14;173(7):1705-1715.e16 [PMID: 29906448]

Grants

  1. R01 MH061675/NIMH NIH HHS
  2. K02 DA032573/NIDA NIH HHS
  3. U01 MH046276/NIMH NIH HHS
  4. R01 MH086135/NIMH NIH HHS
  5. F32 MH122058/NIMH NIH HHS
  6. R21 DA047527/NIDA NIH HHS
  7. R01 MH067257/NIMH NIH HHS
  8. U01 MH079470/NIMH NIH HHS
  9. R01 MH085548/NIMH NIH HHS
  10. R01 MH059586/NIMH NIH HHS
  11. R28 AA012725/NIAAA NIH HHS
  12. MR/L010305/1/Medical Research Council
  13. R01 MH104964/NIMH NIH HHS
  14. R21 DC018098/NIDCD NIH HHS
  15. R01 MH065571/NIMH NIH HHS
  16. U01 MH079469/NIMH NIH HHS
  17. R01 MH060870/NIMH NIH HHS
  18. R01 MH081800/NIMH NIH HHS
  19. R01 MH065558/NIMH NIH HHS
  20. R01 MH059571/NIMH NIH HHS
  21. R01 MH094320/NIMH NIH HHS
  22. R01 MH059565/NIMH NIH HHS
  23. R01 MH065554/NIMH NIH HHS
  24. R01 MH065578/NIMH NIH HHS
  25. R01 MH059587/NIMH NIH HHS
  26. R01 MH065562/NIMH NIH HHS
  27. R01 MH123451/NIMH NIH HHS
  28. U01 MH046289/NIMH NIH HHS
  29. K01 MH113848/NIMH NIH HHS
  30. U01 MH109532/NIMH NIH HHS
  31. I01 BX003341/BLRD VA
  32. R01 MH065588/NIMH NIH HHS
  33. R01 MH059566/NIMH NIH HHS
  34. F32 AA027435/NIAAA NIH HHS
  35. R01 MH059588/NIMH NIH HHS
  36. U01 MH046318/NIMH NIH HHS
  37. R01 MH065707/NIMH NIH HHS
  38. R01 MH060879/NIMH NIH HHS

MeSH Term

Humans
Schizophrenia
Genome-Wide Association Study
Alcoholism
Polymorphism, Single Nucleotide
Genetic Predisposition to Disease
Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

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