title: 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.
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.
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.|Department of Psychiatry, Yale University School of Medicine, 116A2, 950 Campbell Avenue, West Haven, CT, 06516, USA.|VA CT Healthcare Center, New Haven, CT, USA.
authors.forename: Qian
authors.initials: Q
authors.lastname: Wang
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, 116A2, 950 Campbell Avenue, West Haven, CT, 06516, USA.|VA CT Healthcare Center, New Haven, CT, USA.
authors.forename: Renato
authors.initials: R
authors.lastname: Polimanti
authors.affiliation: Department of Psychiatry, Perelman School of Medicine of the University of Pennsylvania and VISN 4 MIRECC, Crescenz VAMC, Philadelphia, PA, USA.
authors.forename: Henry R
authors.initials: HR
authors.lastname: Kranzler
authors.affiliation: Department of Medicine (Biomedical Genetics), Boston University School of Medicine, Boston, MA, USA.|Department of Neurology, Boston University School of Medicine, Boston, MA, USA.|Department of Ophthalmology, Boston University School of Medicine, Boston, MA, USA.|Department of Biostatistics, Boston University School of Public Health, Boston, MA, USA.|Department of Epidemiology, Boston University School of Public Health, Boston, MA, USA.
authors.forename: Lindsay A
authors.initials: LA
authors.lastname: Farrer
authors.affiliation: Program in Computational Biology and Bioinformatics, Yale University, New Haven, CT, USA.|Department of Biostatistics, Yale University School of Public Health, New Haven, CT, USA.|Department of Genetics, Yale University School of Medicine, New Haven, CT, USA.|VA Cooperative Studies Program Coordinating Center, New Haven, CT, USA.
authors.forename: Hongyu
authors.initials: H
authors.lastname: Zhao
authors.affiliation: Department of Psychiatry, Yale University School of Medicine, 116A2, 950 Campbell Avenue, West Haven, CT, 06516, USA. joel.gelernter@yale.edu.|VA CT Healthcare Center, New Haven, CT, USA. joel.gelernter@yale.edu.|Department of Genetics, Yale University School of Medicine, New Haven, CT, USA. joel.gelernter@yale.edu.|Department of Neuroscience, Yale University School of Medicine, New Haven, CT, USA. joel.gelernter@yale.edu.
authors.forename: Joel
authors.identifier: 0000-0002-4067-1859
authors.initials: J
authors.lastname: Gelernter
mesh_terms: D000328:Adult; D015331:Cohort Studies; D005260:Female; D059647:Gene-Environment Interaction; D058685:Genetic Pleiotropy; D055106:Genome-Wide Association Study; D005838:Genotype; D060005:Genotyping Techniques; D015658:HIV Infections / Q000235:genetics*; D006801:Humans; D016014:Linear Models; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D016485:Needle Sharing; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D012309:Risk-Taking; D012559:Schizophrenia / Q000235:genetics*; D047568:Unsafe Sex