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Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions

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Abstract

Schizophrenia (SZ) and HIV infection are serious disorders with a complex phenotypic relationship. Observational studies have described their comorbidity; their genetic correlation is not well studied. We performed extensive analysis in search of common genetic factors for SZ and HIV, and their relationship with risky sexual behavior (RSB). Summary statistics from genome-wide association studies of HIV infection and schizophrenia were obtained and 2379 European Americans were genotyped and assessed for RSB score. Genetic relationships between traits were analyzed in three ways: linkage disequilibrium (LD) score regression to estimate genetic correlation; GPA (Genetic analysis incorporating Pleiotropy and Annotation) to test pleiotropy and identify pleiotropic loci; polygenic risk scores (PRS) of SZ and HIV to predict RSB using linear regression. We found significant pleiotropy (p = 5.31E − 28) and a positive genetic correlation (cor = 0.17, p = 0.002) for SZ and HIV infection. Pleiotropic SNPs with opposite effect directions (antagonistic) and SNPs with the same effect direction (synergistic) were enriched for distinctly different biological functions. SZ PRS computed with antagonistically pleiotropic SNPs consistently predicted RSB score with nominal significance, but SZ PRS based on either synergistically pleiotropic SNPs or all SNPs did not predict RSB. The epidemiologic correlation between schizophrenia and HIV can partly be explained by overlapping genetic risk factors, which are related to risky sexual behavior.

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Acknowledgments

This study was supported in part by Grants RC2 DA028909, R01 DA12690, R01 DA12849, R01 DA18432, R01 AA11330, R01 AA017535, P50 AA12870, R01 GM59507, and R01 DA030976 from the National Institutes of Health. Although unrelated to this work, Dr. Kranzler has been a consultant or advisory board member for Alkermes, Indivior, Lundbeck, and Otsuka. He is also a member of the American Society of Clinical Psychopharmacology’s Alcohol Clinical Trials Initiative, which is supported by AbbVie, Ethypharm, Lilly, Lundbeck, and Pfizer.

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Authors and Affiliations

  1. Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA

    Qian Wang & Hongyu Zhao

  2. Department of Psychiatry, Yale University School of Medicine, 116A2, 950 Campbell Avenue, West Haven, CT, 06516, USA

    Qian Wang, Renato Polimanti & Joel Gelernter

  3. VA CT Healthcare Center, New Haven, CT, USA

    Qian Wang, Renato Polimanti & Joel Gelernter

  4. Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania and VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA

    Henry R. Kranzler

  5. Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA

    Lindsay A. Farrer

  6. Department of Neurology, Boston University School of Medicine, Boston, MA, USA

    Lindsay A. Farrer

  7. Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA

    Lindsay A. Farrer

  8. Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA

    Lindsay A. Farrer

  9. Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA

    Lindsay A. Farrer

  10. Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA

    Hongyu Zhao

  11. Department of Genetics, Yale University School of Medicine, New Haven, CT, USA

    Hongyu Zhao & Joel Gelernter

  12. VA Cooperative Studies Program Coordinating Center, New Haven, CT, USA

    Hongyu Zhao

  13. Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA

    Joel Gelernter

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  1. Qian Wang
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  2. Renato Polimanti
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  3. Henry R. Kranzler
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  4. Lindsay A. Farrer
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  5. Hongyu Zhao
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  6. Joel Gelernter
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Correspondence to Joel Gelernter.

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Dr. Gelernter, Dr. Zhao, Dr. Farrer, Dr. Polimanti, and Qian Wang reported no biomedical financial interests or potential conflicts of interest.

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Wang, Q., Polimanti, R., Kranzler, H.R. et al. Genetic factor common to schizophrenia and HIV infection is associated with risky sexual behavior: antagonistic vs. synergistic pleiotropic SNPs enriched for distinctly different biological functions. Hum Genet 136, 75–83 (2017). https://doi.org/10.1007/s00439-016-1737-8

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