{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T13:19:45Z","timestamp":1768569585451,"version":"3.49.0"},"posted":{"date-parts":[[2025,3,10]]},"group-title":"Psychiatry and Clinical Psychology","reference-count":42,"publisher":"openRxiv","license":[{"start":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T00:00:00Z","timestamp":1741564800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by-nc-nd\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2025,6,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  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 \u2264 5, GERP++ &gt; 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\n                  <jats:italic>KNCN\/MKNK1-AS1<\/jats:italic>\n                  overlap region (odds ratio: 5.1, FDR &lt; 0.05). Expression analysis revealed strong co-expression of these genes in striatal brain regions implicated in OCD pathophysiology. Genes co-expressed with\n                  <jats:italic>KNCN\/MKNK1-AS1<\/jats:italic>\n                  were enriched for synaptic vesicle dynamics, calcium signaling, and established OCD risk genes, highlighting the importance of non-coding regulatory variation in psychiatric genetics.\n                <\/jats:p>","DOI":"10.1101\/2025.03.07.25323592","type":"posted-content","created":{"date-parts":[[2025,3,10]],"date-time":"2025-03-10T23:15:17Z","timestamp":1741648517000},"source":"Crossref","is-referenced-by-count":0,"title":["Rare Variants in Antisense lncRNA-Protein Coding Gene Overlap Regions Contribute to Obsessive-Compulsive Disorder"],"prefix":"10.64898","author":[{"given":"Seulgi","family":"Jung","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Madison","family":"Caballero","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Shelby","family":"Smout","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-6087-9537","authenticated-orcid":false,"given":"Behrang","family":"Mahjani","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2025062708001135000_2025.03.07.25323592v2.1","doi-asserted-by":"publisher","DOI":"10.1038\/mp.2008.94"},{"key":"2025062708001135000_2025.03.07.25323592v2.2","doi-asserted-by":"publisher","DOI":"10.1017\/S0033291721001744"},{"key":"2025062708001135000_2025.03.07.25323592v2.3","doi-asserted-by":"publisher","DOI":"10.1001\/jama.2017.2200"},{"key":"2025062708001135000_2025.03.07.25323592v2.4","first-page":"12","article-title":"Neural substrates of symptoms of obsessive-compulsive disorder in children: a developmental perspective","volume":"223","year":"2023","journal-title":"Br J Psychiatry"},{"key":"2025062708001135000_2025.03.07.25323592v2.5","doi-asserted-by":"publisher","DOI":"10.1001\/archgenpsychiatry.2009.152"},{"key":"2025062708001135000_2025.03.07.25323592v2.6","doi-asserted-by":"crossref","first-page":"1389","DOI":"10.1038\/s41588-025-02189-z","article-title":"Genome-wide analyses identify 30 loci associated with obsessive-compulsive disorder","volume":"57","year":"2025","journal-title":"Nat. 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