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Genome-wide analysis of schizophrenia and multiple sclerosis identifies shared genomic loci with mixed direction of effects.
Ahangari, Mohammad; Everest, Elif; Nguyen, Tan-Hoang; Verrelli, Brian C; Webb, Bradley T; Bacanu, Silviu-Alin; Tahir Turanli, Eda; Riley, Brien P.
Afiliação
  • Ahangari M; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Integrative Life Sciences PhD Program, Virginia Commonwealth University, Richmond, VA, USA. Electronic address: ahangarim@vcu.edu.
  • Everest E; Department of Molecular Biology and Genetics, Istanbul Technical University, Istanbul, Turkey.
  • Nguyen TH; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
  • Verrelli BC; Center for Biological Data Science, Virginia Commonwealth University, Richmond, VA, USA.
  • Webb BT; GenOmics, Bioinformatics, and Translational Research Center, Biostatistics and Epidemiology Division, RTI International, Research Triangle Park, NC, USA.
  • Bacanu SA; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA.
  • Tahir Turanli E; Faculty of Engineering and Natural Sciences, Department of Molecular Biology and Genetics, Acibadem University, Istanbul, Turkey.
  • Riley BP; Virginia Institute for Psychiatric and Behavioral Genetics, Virginia Commonwealth University, Richmond, VA, USA; Department of Psychiatry, Virginia Commonwealth University, Richmond, VA, USA; Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Brain Behav Immun ; 104: 183-190, 2022 Aug.
Article em En | MEDLINE | ID: mdl-35714915
ABSTRACT
Common genetic variants identified in genome-wide association studies (GWAS) show varying degrees of genetic pleiotropy across complex human disorders. Clinical studies of schizophrenia (SCZ) suggest that in addition to neuropsychiatric symptoms, patients with SCZ also show variable immune dysregulation. Epidemiological studies of multiple sclerosis (MS), an autoimmune, neurodegenerative disorder of the central nervous system, suggest that in addition to the manifestation of neuroinflammatory complications, patients with MS may also show co-occurring neuropsychiatric symptoms with disease progression. In this study, we analyzed the largest available GWAS datasets for SCZ (N = 161,405) and MS (N = 41,505) using Gaussian causal mixture modeling (MiXeR) and conditional/conjunctional false discovery rate (condFDR) frameworks to explore and quantify the shared genetic architecture of these two complex disorders at common variant level. Despite detecting only a negligible genetic correlation (rG = 0.057), we observe polygenic overlap between SCZ and MS, and a substantial genetic enrichment in SCZ conditional on associations with MS, and vice versa. By leveraging this cross-disorder enrichment, we identified 36 loci jointly associated with SCZ and MS at conjunctional FDR < 0.05 with mixed direction of effects. Follow-up functional analysis of the shared loci implicates candidate genes and biological processes involved in immune response and B-cell receptor signaling pathways. In conclusion, this study demonstrates the presence of polygenic overlap between SCZ and MS in the absence of a genetic correlation and provides new insights into the shared genetic architecture of these two disorders at the common variant level.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Brain Behav Immun Assunto da revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Ano de publicação: 2022 Tipo de documento: Article

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Tipo de estudo: Prognostic_studies Idioma: En Revista: Brain Behav Immun Assunto da revista: ALERGIA E IMUNOLOGIA / CEREBRO / PSICOFISIOLOGIA Ano de publicação: 2022 Tipo de documento: Article
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