{"doi":"10.1101/2023.10.16.23297073","title":"Genomic insights into the comorbidity between type 2 diabetes and schizophrenia","abstract":"Abstract Multimorbidity represents an increasingly important public health challenge with far-reaching implications for health management and policy. Mental health and metabolic diseases have a well-established epidemiological association. In this study, we investigate the genetic intersection between type 2 diabetes and schizophrenia. We use Mendelian randomization to examine potential causal relationships between the two conditions and related endophenotypes. We report no compelling evidence that type 2 diabetes genetic liability potentially causally influences schizophrenia risk and vice versa . Our findings show that increased body mass index (BMI) has a protective effect against schizophrenia, in contrast to the well-known risk-increasing effect of BMI on type 2 diabetes risk. We identify evidence of colocalization of association signals for these two conditions at 11 genomic loci, six of which have opposing directions of effect for type 2 diabetes and schizophrenia. To elucidate these colocalizing signals, we integrate multi-omics data from bulk and single-cell gene expression studies, along with functional information. We identify high-confidence effector genes and find that they are enriched for homeostasis and lipid-related pathways. We also highlight drug repurposing opportunities including N-methyl-D-aspartate (NMDA) receptor antagonists. Our findings provide insights into shared biological mechanisms for type 2 diabetes and schizophrenia, highlighting common factors that influence the risk of the two conditions in opposite directions and shedding light on the complex nature of this comorbidity.","journal":"medRxiv","year":2023,"id":412638,"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":0.9516,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2023-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":416666,"name":"Golam M. Khandaker","orcid":"0000-0002-4935-9220","position":1,"is_corresponding":false},{"id":16092,"name":"Andrew P. Morris","orcid":"0000-0002-6805-6014","position":2,"is_corresponding":false},{"id":1528,"name":"George Davey Smith","orcid":"0000-0002-1407-8314","position":3,"is_corresponding":false},{"id":35431,"name":"Laura M. Huckins","orcid":"0000-0002-5369-6502","position":4,"is_corresponding":false},{"id":4424,"name":"Eleftheria Zeggini","orcid":"0000-0003-4238-659X","position":5,"is_corresponding":false},{"id":1193410,"name":"Ana Luiza Arruda","orcid":"0000-0002-6550-9794","position":0,"is_corresponding":true}],"reference_count":116,"raw_metadata":{"citation_network_status":"fetched"},"created_at":"2026-07-19T01:21:50.261851Z","pmid":"37905000","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":[]}