{"doi":"10.1101/2025.01.12.632645","title":"Shared Molecular Landscape of Human Brain Structure and Systemic Metabolism","abstract":"Background: brain morphology in the general population. Methods: We performed uni- and multivariate regression on metabolomics and MRI data from 24,940 UK Biobank participants, to estimate the individual and combined associations of 249 circulating metabolic markers with 91 measures of global and regional cortical thickness, surface area and subcortical volume. We investigated similarity of the identified spatial patterns with brain maps of neurotransmitters, and used Mendelian randomization to uncover causal relationships between metabolites and the brain. Results: Intracranial volume and total surface area were highly significantly associated with circulating lipoproteins and glycoprotein acetyls, with correlations up to .15. There were strong regional associations of individual markers with mixed effect directions, with distinct patterns involving frontal and temporal cortical thickness, brainstem and ventricular volume. Mendelian randomization provided evidence of bidirectional causal effects, with the majority of markers affecting frontal and temporal regions. Discussion: The results indicate strong bidirectional causal relationships between circulating metabolic markers and distinct patterns of global and regional brain morphology. The generated atlas of associations provides a better understanding of the role of metabolic pathways in structural brain development and maintenance, in both health and disease.","journal":"bioRxiv (Cold Spring Harbor Laboratory)","year":2025,"id":560355,"datarank":0.0,"base_score":0.0,"endowment":0.0,"self_citation_contribution":0.0,"citation_network_contribution":0.0,"self_endowment_contribution":0.0,"citer_contribution":0.0,"corpus_percentile":null,"corpus_rank":null,"citation_count":0,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.8209,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2025-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":942336,"name":"Jakub Kopál","orcid":"0000-0002-1201-2872","position":1,"is_corresponding":false},{"id":1023174,"name":"Sara Stinson","orcid":"0000-0002-1491-9179","position":2,"is_corresponding":false},{"id":1462591,"name":"Olav Smeland","orcid":null,"position":3,"is_corresponding":false},{"id":34326,"name":"Alexey Shadrin","orcid":"0000-0002-7467-250X","position":4,"is_corresponding":false},{"id":1328745,"name":"Julian Fuhrer","orcid":"0000-0001-6286-5614","position":5,"is_corresponding":false},{"id":352267,"name":"Jaroslav Rokicki","orcid":null,"position":6,"is_corresponding":false},{"id":1462592,"name":"Tiril Gurholt","orcid":null,"position":7,"is_corresponding":false},{"id":1462593,"name":"Ida Sonderby","orcid":null,"position":8,"is_corresponding":false},{"id":1462594,"name":"Ibrahim Akkouh","orcid":null,"position":9,"is_corresponding":false},{"id":112330,"name":"Oleksandr Frei","orcid":null,"position":10,"is_corresponding":false},{"id":1462595,"name":"Kevin O'Connell","orcid":null,"position":11,"is_corresponding":false},{"id":246433,"name":"Lars T. Westlye","orcid":"0000-0001-8644-956X","position":12,"is_corresponding":false},{"id":279140,"name":"Srdjan Djurovic","orcid":"0000-0002-8140-8061","position":13,"is_corresponding":false},{"id":19608,"name":"Anders M. Dale","orcid":"0000-0002-6126-2966","position":14,"is_corresponding":false},{"id":52934,"name":"Ole A. Andreassen","orcid":"0000-0002-4461-3568","position":15,"is_corresponding":false},{"id":246427,"name":"Dennis van der Meer","orcid":"0000-0002-0466-386X","position":0,"is_corresponding":true}],"reference_count":55,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T02:55:42.883572Z","pmid":"39868214","pmcid":null,"fwci":null,"citation_percentile":null,"influential_citations":0,"oa_status":null,"license":null,"views":0,"total_file_size_bytes":0,"version_count":0,"fair_f":null,"fair_a":null,"fair_i":null,"fair_r":null,"fair_zscore":null,"fair_rationale":null,"fair_model":null,"fair_agent_version":null,"fair_fulltext_source":null,"fair_has_llm":null,"fair_computed_at":null,"clinical_trials":[],"software_tools":[],"db_accessions":[],"linked_datasets":[],"topics":[]}