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Association between substance use disorder and polygenic liability to schizophrenia

Sarah M. Hartz, Amy Horton, Mary Oehlert, Caitlin E. Carey, Arpana Agrawal, Ryan Bogdan, Li-Shiun Chen, Dana B. Hancock, Eric O. Johnson, Carlos Pato, Michele Pato, John P. Rice, Laura J. Bierut
doi: https://doi.org/10.1101/129288
Sarah M. Hartz
Washington University in St. Louis, MO, USA
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Amy Horton
Washington University in St. Louis, MO, USA
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Mary Oehlert
VA Eastern Kansas Health Care System, Leavenworth, KS, USAThe University of Kansas Medical Center, Kansas City, KS, USA
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Caitlin E. Carey
Washington University in St. Louis, MO, USA
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Arpana Agrawal
Washington University in St. Louis, MO, USA
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Ryan Bogdan
Washington University in St. Louis, MO, USA
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Li-Shiun Chen
Washington University in St. Louis, MO, USA
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Dana B. Hancock
RTI International, Research Triangle Park, NC, USA
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Eric O. Johnson
RTI International, Research Triangle Park, NC, USA
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Carlos Pato
SUNY Downstate Medical Center, Brooklyn, NY, USA
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Michele Pato
SUNY Downstate Medical Center, Brooklyn, NY, USA
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John P. Rice
Washington University in St. Louis, MO, USA
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Laura J. Bierut
Washington University in St. Louis, MO, USA
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Abstract

Background There are high levels of comorbidity between schizophrenia and substance use disorder, but little is known about the genetic etiology of this comorbidity.

Methods Here, we test the hypothesis that shared genetic liability contributes to the high rates of comorbidity between schizophrenia and substance use disorder. To do this, polygenic risk scores for schizophrenia derived from a large meta-analysis by the Psychiatric Genomics Consortium were computed in three substance use disorder datasets: COGEND (ascertained for nicotine dependence n=918 cases, 988 controls), COGA (ascertained for alcohol dependence n=643 cases, 384 controls), and FSCD (ascertained for cocaine dependence n=210 cases, 317 controls). Phenotypes were harmonized across the three datasets and standardized analyses were performed. Genome-wide genotypes were imputed to 1000 Genomes reference panel.

Results In each individual dataset and in the mega-analysis, strong associations were observed between any substance use disorder diagnosis and the polygenic risk score for schizophrenia (mega-analysis pseudo R2 range 0.8%-3.7%, minimum p=4×10-23).

Conclusions These results suggest that comorbidity between schizophrenia and substance use disorder is partially attributable to shared polygenic liability. This shared liability is most consistent with a general risk for substance use disorder rather than specific risks for individual substance use disorders and adds to increasing evidence of a blurred boundary between schizophrenia and substance use disorder.

Footnotes

  • The authors have no relevant conflicts of interest. Funding was provided by the NIH and NSF.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. It is made available under a CC-BY-NC-ND 4.0 International license.
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Posted April 21, 2017.
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Association between substance use disorder and polygenic liability to schizophrenia
Sarah M. Hartz, Amy Horton, Mary Oehlert, Caitlin E. Carey, Arpana Agrawal, Ryan Bogdan, Li-Shiun Chen, Dana B. Hancock, Eric O. Johnson, Carlos Pato, Michele Pato, John P. Rice, Laura J. Bierut
bioRxiv 129288; doi: https://doi.org/10.1101/129288
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Association between substance use disorder and polygenic liability to schizophrenia
Sarah M. Hartz, Amy Horton, Mary Oehlert, Caitlin E. Carey, Arpana Agrawal, Ryan Bogdan, Li-Shiun Chen, Dana B. Hancock, Eric O. Johnson, Carlos Pato, Michele Pato, John P. Rice, Laura J. Bierut
bioRxiv 129288; doi: https://doi.org/10.1101/129288

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