{"doi":"10.1101/2025.03.07.25323592","title":"Rare Variants in Antisense lncRNA-Protein Coding Gene Overlap Regions Contribute to Obsessive-Compulsive Disorder","abstract":"Abstract Obsessive-compulsive disorder (OCD) is a prevalent neuropsychiatric disorder with an incompletely understood genetic basis, limiting targeted therapeutic options. Although previous rare variant studies have primarily focused on protein-coding genes, the contribution of rare regulatory non-coding variants remains largely unexplored. We analyzed whole-genome sequencing data from 2,561 OCD cases and 12,974 controls from the All of Us Research Program to investigate rare, conserved variants (minor allele count ≤ 5, GERP++ > 0) within antisense long non-coding RNA (lncRNA) and protein-coding gene overlap regions. A burden analysis identified a significant association with OCD in the KNCN/MKNK1-AS1 overlap region (odds ratio: 5.1, FDR < 0.05). Expression analysis revealed strong co-expression of these genes in striatal brain regions implicated in OCD pathophysiology. Genes co-expressed with KNCN/MKNK1-AS1 were enriched for synaptic vesicle dynamics, calcium signaling, and established OCD risk genes, highlighting the importance of non-coding regulatory variation in psychiatric genetics.","journal":"medRxiv","year":2025,"id":562882,"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":0.9296,"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":269786,"name":"Madison Caballero","orcid":"0000-0002-4499-5105","position":1,"is_corresponding":false},{"id":1465758,"name":"Shelby Smout","orcid":null,"position":2,"is_corresponding":false},{"id":104445,"name":"Behrang Mahjani","orcid":"0000-0001-6087-9537","position":3,"is_corresponding":false},{"id":1030749,"name":"Seulgi Jung","orcid":"0000-0002-7264-4310","position":0,"is_corresponding":true}],"reference_count":39,"raw_metadata":null,"created_at":"2026-07-19T02:56:09.638214Z","pmid":"40666340","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":[]}