{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\n Two independent genome‐wide studies"}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": "have implicated the long intergenic non‐protein coding RNA LINC01360 in the pathogenesis of major depressive disorder (MDD). In one study, SNPs located in a gene‐dense region on chromosome 1 that includes LINC01360 were found to be associated specifically with MDD, thereby nominating this locus as a potential risk factor for the condition."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "1"}]}, {"type": "t", "text": " In a more detailed functional follow‐up, a human‐unique Alu insertion polymorphism (rs70959274) in the 5′ flanking region of LINC01360 was shown to act as a transcriptional silencer, likely by modulating CpG methylation within the region. The risk allele linked with MDD is almost invariably associated with the absence of this Alu insertion, which results in a higher baseline transcriptional activity of LINC01360. Functional assays—including luciferase reporter studies and CRISPR/Cas9-directed deletion experiments—demonstrated that removal of the Alu element leads not only to increased LINC01360 expression but also to dysregulation of downstream genes and pathways relevant to neuronal signaling, synaptic transmission, neurogenesis, and the PI3K-Akt pathway."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}]}, {"type": "t", "text": " These results suggest that proper transcriptional regulation of LINC01360 is important for maintaining gene expression programs critical to neuronal function and that its dysregulation may contribute to MDD susceptibility.\n "}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Keira J A Johnston, Mark J Adams, Barbara I Nicholl, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of novel common variants associated with chronic pain using conditional false discovery rate analysis with major depressive disorder and assessment of pleiotropic effects of LRFN5."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Psychiatry (2019)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41398-019-0613-4"}], "href": "https://doi.org/10.1038/s41398-019-0613-4"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "31748543"}], "href": "https://pubmed.ncbi.nlm.nih.gov/31748543"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Weipeng Liu, Wenqiang Li, Xin Cai, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of a functional human-unique 351-bp Alu insertion polymorphism associated with major depressive disorder in the 1p31.1 GWAS risk loci."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Neuropsychopharmacology (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41386-020-0659-2"}], "href": "https://doi.org/10.1038/s41386-020-0659-2"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32193514"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32193514"}]}]}]}