Shared genetics linking sociability with the brain's default mode network.

Autor:	Fanelli G; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands., Robinson J; Global Computational Biology and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany., Fabbri C; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy., Bralten J; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands., Roth Mota N; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands., Arenella M; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Forensic and Neurodevelopmental Science, Institute of Psychiatry, Psychology and Neuroscience, King's College, London, UK., Sprooten E; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands., Franke B; Department of Human Genetics, Donders Institute for Brain, Cognition and Behaviour, Radboud University Medical Center, Nijmegen, The Netherlands.; Department of Cognitive Neuroscience, Donders Institute for Brain, Cognition and Behavior, Radboud University Medical Center, Nijmegen, The Netherlands., Kas M; Groningen Institute for Evolutionary Life Sciences, University of Groningen, Groningen, The Netherlands., Andlauer TF; Global Computational Biology and Data Sciences, Boehringer Ingelheim Pharma GmbH & Co. KG, Biberach an der Riß, Germany.; Department of Neurology, Klinikum rechts der Isar, School of Medicine, Technical University of Munich, Munich, Germany., Serretti A; Department of Biomedical and Neuromotor Sciences, University of Bologna, Bologna, Italy.; Department of Medicine and Surgery, Kore University of Enna, Enna, Italy.
Jazyk:	angličtina
Zdroj:	MedRxiv : the preprint server for health sciences [medRxiv] 2024 May 25. Date of Electronic Publication: 2024 May 25.
DOI:	10.1101/2024.05.24.24307883
Abstrakt:	The brain's default mode network (DMN) plays a role in social cognition, with altered DMN function being associated with social impairments across various neuropsychiatric disorders. In the present study, we examined the genetic relationship between sociability and DMN-related resting-state functional magnetic resonance imaging (rs-fMRI) traits. To this end, we used genome-wide association summary statistics for sociability and 31 activity and 64 connectivity DMN-related rs-fMRI traits (N=34,691-342,461). First, we examined global and local genetic correlations between sociability and the rs-fMRI traits. Second, to assess putatively causal relationships between the traits, we conducted bi-directional Mendelian randomisation (MR) analyses. Finally, we prioritised genes influencing both sociability and rs-fMRI traits by combining three methods: gene-expression eQTL MR analyses, the CELLECT framework using single-nucleus RNA-seq data, and network propagation in the context of a protein-protein interaction network. Significant local genetic correlations were found between sociability and two rs-fMRI traits, one representing spontaneous activity within the temporal cortex, the other representing connectivity between the frontal/cingulate and angular/temporal cortices. Sociability affected 12 rs-fMRI traits when allowing for weakly correlated genetic instruments. Combing all three methods for gene prioritisation, we defined 17 highly prioritised genes, with DRD2 and LINGO1 showing the most robust evidence across all analyses. By integrating genetic and transcriptomics data, our gene prioritisation strategy may serve as a blueprint for future studies. The prioritised genes could be explored as potential biomarkers for social dysfunction in the context of neuropsychiatric disorders and as drug target genes. Competing Interests: AS is or has been a consultant/speaker for Abbott, Abbvie, Angelini, AstraZeneca, Clinical Data, Boehringer Ingelheim, Bristol-Myers Squibb, Eli Lilly, GlaxoSmithKline, Innovapharma, Italfarmaco, Janssen, Lundbeck, Naurex, Pfizer, Polifarma, Sanofi, Servier and Taliaz. BF discloses having received educational speaking fees and travel support from Medice. CF was a speaker for Janssen. All other authors report no biomedical financial interests or potential conflicts of interest.
Databáze:	MEDLINE
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