Articles producció científica> Bioquímica i Biotecnologia

Local patterns of genetic sharing between neuropsychiatric and insulin resistance-related conditions

  • Datos identificativos

    Identificador: imarina:9452190
    Handle: https://hdl.handle.net/20.500.11797/imarina9452190
    Autores:
    Fanelli, GiuseppeFranke, BarbaraFabbri, ChiaraWerme, JosefinErdogan, IzelDe Witte, WardPoelmans, GeertRuisch, I HyunReus, Lianne Mariavan Gils, VeerleJansen, Willemijn JVos, Stephanie J BAlam, Kazi AsrafulMartinez, AuroraHaavik, JanWimberley, TheresaDalsgaard, SorenFothi, AbelBarta, CsabaFernandez-Aranda, FernandoJimenez-Murcia, SusanaBerkel, SimoneMatura, SilkeSalas-Salvado, JordiArenella, MartinaSerretti, AlessandroMota, Nina RothBralten, Janita
    Resumen:
    The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a major public health challenge. Evidence of the genetic links between these phenotypes is emerging, but little is currently known about the genomic regions and biological functions that are involved. To address this, we performed Local Analysis of [co]Variant Association (LAVA) using large-scale (N = 9,725-933,970) genome-wide association studies (GWASs) results for three IR-related conditions (type 2 diabetes mellitus, obesity, and metabolic syndrome) and nine neuropsychiatric disorders. Subsequently, positional and expression quantitative trait locus (eQTL)-based gene mapping and downstream functional genomic analyses were performed on the significant loci. Patterns of negative and positive local genetic correlations (|r(g)| = 0.21-1, pFDR < 0.05) were identified at 109 unique genomic regions across all phenotype pairs. Local correlations emerged even in the absence of global genetic correlations between IR-related conditions and Alzheimer's disease, bipolar disorder, and Tourette's syndrome. Genes mapped to the correlated regions showed enrichment in biological pathways integral to immune-inflammatory function, vesicle trafficking, insulin signalling, oxygen transport, and lipid metabolism. Colocalisation analyses further prioritised 10 genetically correlated regions for likely harbouring shared causal variants, displaying high deleterious or regulatory potential. These variants were found within or in close proximity to genes, such as SLC39A8 and HLA-DRB1, that can be targeted by supplements and already known drugs, including omega-3/6 fatty acids, immunomodulatory, antihypertensive, and cholesterol-lowering drugs. Overall, our findings highlight the complex

  • Otros:

    Autor según el artículo: Fanelli, Giuseppe; Franke, Barbara; Fabbri, Chiara; Werme, Josefin; Erdogan, Izel; De Witte, Ward; Poelmans, Geert; Ruisch, I Hyun; Reus, Lianne Maria; van Gils, Veerle; Jansen, Willemijn J; Vos, Stephanie J B; Alam, Kazi Asraful; Martinez, Aurora; Haavik, Jan; Wimberley, Theresa; Dalsgaard, Soren; Fothi, Abel; Barta, Csaba; Fernandez-Aranda, Fernando; Jimenez-Murcia, Susana; Berkel, Simone; Matura, Silke; Salas-Salvado, Jordi; Arenella, Martina; Serretti, Alessandro; Mota, Nina Roth; Bralten, Janita
    Departamento: Bioquímica i Biotecnologia
    Autor/es de la URV: Salas Salvadó, Jorge
    Palabras clave: Zinc-sulfate Quantitative trait loci Phenotype Obesity Metabolic syndrome Mental disorders Management Lin Insulin resistance Humans Genome-wide association study Genetic predisposition to disease Extracellular-matrix Double-blind Disorders Diabetes mellitus, type 2 Bcl11a
    Resumen: The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a major public health challenge. Evidence of the genetic links between these phenotypes is emerging, but little is currently known about the genomic regions and biological functions that are involved. To address this, we performed Local Analysis of [co]Variant Association (LAVA) using large-scale (N = 9,725-933,970) genome-wide association studies (GWASs) results for three IR-related conditions (type 2 diabetes mellitus, obesity, and metabolic syndrome) and nine neuropsychiatric disorders. Subsequently, positional and expression quantitative trait locus (eQTL)-based gene mapping and downstream functional genomic analyses were performed on the significant loci. Patterns of negative and positive local genetic correlations (|r(g)| = 0.21-1, pFDR < 0.05) were identified at 109 unique genomic regions across all phenotype pairs. Local correlations emerged even in the absence of global genetic correlations between IR-related conditions and Alzheimer's disease, bipolar disorder, and Tourette's syndrome. Genes mapped to the correlated regions showed enrichment in biological pathways integral to immune-inflammatory function, vesicle trafficking, insulin signalling, oxygen transport, and lipid metabolism. Colocalisation analyses further prioritised 10 genetically correlated regions for likely harbouring shared causal variants, displaying high deleterious or regulatory potential. These variants were found within or in close proximity to genes, such as SLC39A8 and HLA-DRB1, that can be targeted by supplements and already known drugs, including omega-3/6 fatty acids, immunomodulatory, antihypertensive, and cholesterol-lowering drugs. Overall, our findings highlight the complex genetic architecture of IR-neuropsychiatric multimorbidity, advocating for an integrated disease model and offering novel insights for research and treatment strategies in this domain.
    Grupo de investigación: Alimentació, Nutrició, Desenvolupament i Salut Mental
    Áreas temáticas: Saúde coletiva Psychiatry and mental health Psychiatry Psicología Nutrição Medicina ii Medicina i Linguística e literatura Interdisciplinar Engenharias iv Enfermagem Educação física Ciências biológicas ii Ciências biológicas i Cellular and molecular neuroscience Biotecnología Biological psychiatry
    Acceso a la licencia de uso: https://creativecommons.org/licenses/by/3.0/es/
    Direcció de correo del autor: jordi.salas@urv.cat
    Identificador del autor: 0000-0003-2700-7459
    Fecha de alta del registro: 2025-04-30
    Versión del articulo depositado: info:eu-repo/semantics/publishedVersion
    Referencia al articulo segun fuente origial: Translational Psychiatry. 15 (1): 145-
    Referencia de l'ítem segons les normes APA: Fanelli, Giuseppe; Franke, Barbara; Fabbri, Chiara; Werme, Josefin; Erdogan, Izel; De Witte, Ward; Poelmans, Geert; Ruisch, I Hyun; Reus, Lianne Maria (2025). Local patterns of genetic sharing between neuropsychiatric and insulin resistance-related conditions. Translational Psychiatry, 15(1), 145-. DOI: 10.1038/s41398-025-03349-9
    URL Documento de licencia: https://repositori.urv.cat/ca/proteccio-de-dades/
    Entidad: Universitat Rovira i Virgili
    Año de publicación de la revista: 2025
    Tipo de publicación: Journal Publications

  • Palabras clave:

    Biological Psychiatry,Cellular and Molecular Neuroscience,Psychiatry,Psychiatry and Mental Health
    Zinc-sulfate
    Quantitative trait loci
    Phenotype
    Obesity
    Metabolic syndrome
    Mental disorders
    Management
    Lin
    Insulin resistance
    Humans
    Genome-wide association study
    Genetic predisposition to disease
    Extracellular-matrix
    Double-blind
    Disorders
    Diabetes mellitus, type 2
    Bcl11a
    Saúde coletiva
    Psychiatry and mental health
    Psychiatry
    Psicología
    Nutrição
    Medicina ii
    Medicina i
    Linguística e literatura
    Interdisciplinar
    Engenharias iv
    Enfermagem
    Educação física
    Ciências biológicas ii
    Ciências biológicas i
    Cellular and molecular neuroscience
    Biotecnología
    Biological psychiatry

  • Documentos:

    DocumentPrincipal

  • Cerca a google

    Search to google scholar