Local patterns of genetic sharing between neuropsychiatric and insulin resistance-related conditions DOI Creative Commons
Giuseppe Fanelli, Barbara Franke, Chiara Fabbri

et al.

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 12, 2025

The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a major public health challenge. Evidence the genetic links between these phenotypes emerging, but little currently known about genomic regions and biological functions that are involved. To address this, we performed Local Analysis [co]Variant Association (LAVA) using large-scale (N = 9,725-933,970) genome-wide association studies (GWASs) results for three IR-related (type 2 diabetes mellitus, obesity, syndrome) nine disorders. Subsequently, positional expression quantitative trait locus (eQTL)-based gene mapping downstream functional analyses were on significant loci. Patterns negative positive local correlations (|rg| 0.21-1, pFDR < 0.05) identified at 109 unique across all phenotype pairs. emerged even in absence global Alzheimer's disease, bipolar disorder, Tourette's syndrome. Genes mapped to correlated showed enrichment pathways integral immune-inflammatory function, vesicle trafficking, signalling, oxygen transport, lipid metabolism. Colocalisation further prioritised 10 genetically likely harbouring shared causal variants, displaying high deleterious or regulatory potential. These variants found within close proximity genes, such as SLC39A8 HLA-DRB1, can be targeted by supplements already drugs, including omega-3/6 fatty acids, immunomodulatory, antihypertensive, cholesterol-lowering drugs. Overall, our findings highlight complex architecture IR-neuropsychiatric multimorbidity, advocating an integrated disease model offering novel insights research treatment strategies this domain.

Language: Английский

Local patterns of genetic sharing between neuropsychiatric and insulin resistance-related conditions DOI Creative Commons
Giuseppe Fanelli, Barbara Franke, Chiara Fabbri

et al.

Translational Psychiatry, Journal Year: 2025, Volume and Issue: 15(1)

Published: April 12, 2025

The co-occurrence of insulin resistance (IR)-related metabolic conditions with neuropsychiatric disorders is a major public health challenge. Evidence the genetic links between these phenotypes emerging, but little currently known about genomic regions and biological functions that are involved. To address this, we performed Local Analysis [co]Variant Association (LAVA) using large-scale (N = 9,725-933,970) genome-wide association studies (GWASs) results for three IR-related (type 2 diabetes mellitus, obesity, syndrome) nine disorders. Subsequently, positional expression quantitative trait locus (eQTL)-based gene mapping downstream functional analyses were on significant loci. Patterns negative positive local correlations (|rg| 0.21-1, pFDR < 0.05) identified at 109 unique across all phenotype pairs. emerged even in absence global Alzheimer's disease, bipolar disorder, Tourette's syndrome. Genes mapped to correlated showed enrichment pathways integral immune-inflammatory function, vesicle trafficking, signalling, oxygen transport, lipid metabolism. Colocalisation further prioritised 10 genetically likely harbouring shared causal variants, displaying high deleterious or regulatory potential. These variants found within close proximity genes, such as SLC39A8 HLA-DRB1, can be targeted by supplements already drugs, including omega-3/6 fatty acids, immunomodulatory, antihypertensive, cholesterol-lowering drugs. Overall, our findings highlight complex architecture IR-neuropsychiatric multimorbidity, advocating an integrated disease model offering novel insights research treatment strategies this domain.

Language: Английский

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