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Associations between antagonistic SNPs for neuropsychiatric disorders and human brain structure.
Federmann, Lydia M; David, Friederike S; Jockwitz, Christiane; Mühleisen, Thomas W; Pelzer, Dominique I; Nöthen, Markus M; Caspers, Svenja; Amunts, Katrin; Goltermann, Janik; Andlauer, Till F M; Stein, Frederike; Brosch, Katharina; Kircher, Tilo; Cichon, Sven; Dannlowski, Udo; Sindermann, Lisa; Forstner, Andreas J.
Afiliação
  • Federmann LM; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany. l.federmann@fz-juelich.de.
  • David FS; Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany. l.federmann@fz-juelich.de.
  • Jockwitz C; Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
  • Mühleisen TW; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
  • Pelzer DI; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
  • Nöthen MM; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
  • Caspers S; Cécile and Oskar Vogt Institute for Brain Research, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
  • Amunts K; Department of Biomedicine, University of Basel, Basel, Switzerland.
  • Goltermann J; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
  • Andlauer TFM; Institute of Human Genetics, University of Bonn, School of Medicine & University Hospital Bonn, Bonn, Germany.
  • Stein F; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
  • Brosch K; Institute for Anatomy I, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
  • Kircher T; Institute of Neuroscience and Medicine (INM-1), Research Centre Jülich, Jülich, Germany.
  • Cichon S; Cécile and Oskar Vogt Institute for Brain Research, Medical Faculty & University Hospital Düsseldorf, Heinrich Heine University, Düsseldorf, Germany.
  • Dannlowski U; Institute for Translational Psychiatry, University of Münster, Münster, Germany.
  • Sindermann L; Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany.
  • Forstner AJ; Department of Psychiatry and Psychotherapy, Philipps-University and University Hospital Marburg, Marburg, Germany.
Transl Psychiatry ; 14(1): 406, 2024 Oct 02.
Article em En | MEDLINE | ID: mdl-39358328
ABSTRACT
A previously published genome-wide association study (GWAS) meta-analysis across eight neuropsychiatric disorders identified antagonistic single-nucleotide polymorphisms (SNPs) at eleven genomic loci where the same allele was protective against one neuropsychiatric disorder and increased the risk for another. Until now, these antagonistic SNPs have not been further investigated regarding their link to brain structural phenotypes. Here, we explored their associations with cortical surface area and cortical thickness (in 34 brain regions and one global measure each) as well as the volumes of eight subcortical structures using summary statistics of large-scale GWAS of brain structural phenotypes. We assessed if significantly associated brain structural phenotypes were previously reported to be associated with major neuropsychiatric disorders in large-scale case-control imaging studies by the ENIGMA consortium. We further characterized the effects of the antagonistic SNPs on gene expression in brain tissue and their association with additional cognitive and behavioral phenotypes, and performed an exploratory voxel-based whole-brain analysis in the FOR2107 study (n = 754 patients with major depressive disorder and n = 847 controls). We found that eight antagonistic SNPs were significantly associated with brain structural phenotypes in regions such as anterior parts of the cingulate cortex, the insula, and the superior temporal gyrus. Case-control differences in implicated brain structural phenotypes have previously been reported for bipolar disorder, major depressive disorder, and schizophrenia. In addition, antagonistic SNPs were associated with gene expression changes in brain tissue and linked to several cognitive-behavioral traits. In our exploratory whole-brain analysis, we observed significant associations of gray matter volume in the left superior temporal pole and left superior parietal region with the variants rs301805 and rs1933802, respectively. Our results suggest that multiple antagonistic SNPs for neuropsychiatric disorders are linked to brain structural phenotypes. However, to further elucidate these findings, future case-control genomic imaging studies are required.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Polimorfismo de Nucleotídeo Único / Transtorno Depressivo Maior / Estudo de Associação Genômica Ampla Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Transl Psychiatry Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Estados Unidos
Texto completo
Adicionar na Minha BVS
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Polimorfismo de Nucleotídeo Único / Transtorno Depressivo Maior / Estudo de Associação Genômica Ampla Limite: Adult / Female / Humans / Male / Middle aged Idioma: En Revista: Transl Psychiatry Ano de publicação: 2024 Tipo de documento: Article País de afiliação: Alemanha País de publicação: Estados Unidos