{"doi":"10.3390/jpm12030412","title":"Multi-Omics Characterization of Early- and Adult-Onset Major Depressive Disorder","abstract":"Age at depressive onset (AAO) corresponds to unique symptomatology and clinical outcomes. Integration of genome-wide association study (GWAS) results with additional “omic” measures to evaluate AAO has not been reported and may reveal novel markers of susceptibility and/or resistance to major depressive disorder (MDD). To address this gap, we integrated genomics with metabolomics using data-driven network analysis to characterize and differentiate MDD based on AAO. This study first performed two GWAS for AAO as a continuous trait in (a) 486 adults from the Pharmacogenomic Research Network-Antidepressant Medication Pharmacogenomic Study (PGRN-AMPS), and (b) 295 adults from the Combining Medications to Enhance Depression Outcomes (CO-MED) study. Variants from top signals were integrated with 153 p180-assayed metabolites to establish multi-omics network characterizations of early (<age 18) and adult-onset depression. The most significant variant (p = 8.77 × 10−8) localized to an intron of SAMD3. In silico functional annotation of top signals (p < 1 × 10−5) demonstrated gene expression enrichment in the brain and during embryonic development. Network analysis identified differential associations between four variants (in/near INTU, FAT1, CNTN6, and TM9SF2) and plasma metabolites (phosphatidylcholines, carnitines, biogenic amines, and amino acids) in early- compared with adult-onset MDD. Multi-omics integration identified differential biosignatures of early- and adult-onset MDD. These biosignatures call for future studies to follow participants from childhood through adulthood and collect repeated -omics and neuroimaging measures to validate and deeply characterize the biomarkers of susceptibility and/or resistance to MDD development.","journal":"Journal of Personalized Medicine","year":2022,"id":268984,"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":17,"citer_count":0,"citers_with_citation_signal":0,"citers_with_endowment":0,"datacite_reuse_total":0,"is_dataset":false,"is_dataset_confidence":0.947,"is_data_producer":false,"deposit_databanks":null,"is_oa":true,"file_count":0,"downloads":0,"has_version_chain":false,"published_date":"2022-01-01","fair_score":null,"fair_percentile":null,"algorithm_id":"datarank_citation_only_1hop_v6","ranking_scope":"data_only","authors":[{"id":307082,"name":"Erin F. Barreto","orcid":"0000-0002-0996-1487","position":1,"is_corresponding":false},{"id":931701,"name":"Rakesh Kumar","orcid":"0000-0002-3916-9263","position":2,"is_corresponding":false},{"id":75183,"name":"Rima Kaddurah‐Daouk","orcid":"0000-0003-1858-5732","position":3,"is_corresponding":false},{"id":557271,"name":"Michelle Skime","orcid":"0000-0001-7863-3017","position":4,"is_corresponding":false},{"id":411134,"name":"Taryn L. Mayes","orcid":"0000-0002-5992-6081","position":5,"is_corresponding":false},{"id":330996,"name":"Thomas Carmody","orcid":"0000-0003-3256-8269","position":6,"is_corresponding":false},{"id":40725,"name":"Joanna M. Biernacka","orcid":"0000-0001-9350-4440","position":7,"is_corresponding":false},{"id":228987,"name":"Liewei Wang","orcid":"0000-0003-3818-8531","position":8,"is_corresponding":false},{"id":270363,"name":"Richard M. Weinshilboum","orcid":"0000-0002-4911-7985","position":9,"is_corresponding":false},{"id":241403,"name":"Madhukar H. Trivedi","orcid":"0000-0002-2983-1110","position":10,"is_corresponding":false},{"id":667584,"name":"William V. Bobo","orcid":"0000-0002-5674-3079","position":11,"is_corresponding":false},{"id":294680,"name":"Paul E. Croarkin","orcid":"0000-0001-6843-6503","position":12,"is_corresponding":false},{"id":388473,"name":"Arjun P. Athreya","orcid":"0000-0001-9764-1768","position":13,"is_corresponding":false},{"id":667583,"name":"Caroline W. Grant","orcid":"0000-0001-9342-2138","position":0,"is_corresponding":true}],"reference_count":110,"raw_metadata":null,"created_at":"2026-07-19T00:27:18.142851Z","pmid":"35330412","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":[]}