{"type": "root", "children": [{"type": "p", "children": [{"type": "t", "text": "\nRecent genomic investigations have implicated TMEM161B in neuropsychiatric disorders. Large‐scale genome‐wide association studies have identified variants within the TMEM161B–MEF2C region that associate with major depressive disorder and related psychiatric phenotypes. In these studies, self‐reported clinical diagnoses of depression as well as differences in neural responses during reward and loss anticipation—especially in alcohol dependence cohorts—point to a potential role for TMEM161B in the modulation of neuronal function and affective regulation."}, {"type": "fg", "children": [{"type": "fg_fs", "start_ref": "1", "end_ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nAdditional studies have explored how genetic variants in TMEM161B may interact with personality traits to influence depression risk. One investigation reported that a common risk variant is associated not only with altered striatal activation during reward and loss anticipation but also with an interaction effect involving paranoid personality traits and depressive symptom severity. Furthermore, mediational analyses in related patient cohorts suggest that such genetic factors might exert their influence indirectly through personality dimensions, thereby contributing to the complex etiology of depressive symptoms."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "2"}, {"type": "fg_f", "ref": "4"}, {"type": "fg_f", "ref": "3"}]}, {"type": "t", "text": "\n"}]}, {"type": "t", "text": "\n\n"}, {"type": "p", "children": [{"type": "t", "text": "\nMechanistic studies have begun to unravel the biological function of TMEM161B in neurodevelopment. It encodes an evolutionarily conserved, novel eight‐pass transmembrane protein that plays a critical role in cortical formation. Experimental models, including knockout mice and patient‐derived brain organoids, have demonstrated that disruptions in TMEM161B lead to defects in apical cell polarity and radial glial scaffolding. Functionally, TMEM161B modulates actin-rich filopodia dynamics, acting upstream of the Rho-GTPase CDC42, and its perturbation is linked to severe cortical malformations such as polymicrogyria and intellectual disability."}, {"type": "fg", "children": [{"type": "fg_f", "ref": "5"}]}, {"type": "t", "text": "\n"}]}, {"type": "rg", "children": [{"type": "r", "ref": 1, "children": [{"type": "t", "text": "Craig L Hyde, Michael W Nagle, Chao Tian, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Identification of 15 genetic loci associated with risk of major depression in individuals of European descent."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Nat Genet (2016)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/ng.3623"}], "href": "https://doi.org/10.1038/ng.3623"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "27479909"}], "href": "https://pubmed.ncbi.nlm.nih.gov/27479909"}]}, {"type": "r", "ref": 2, "children": [{"type": "t", "text": "Christine Muench, Melanie Schwandt, Jeesun Jung, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The major depressive disorder GWAS-supported variant rs10514299 in TMEM161B-MEF2C predicts putamen activation during reward processing in alcohol dependence."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Transl Psychiatry (2018)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41398-018-0184-9"}], "href": "https://doi.org/10.1038/s41398-018-0184-9"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "30006604"}], "href": "https://pubmed.ncbi.nlm.nih.gov/30006604"}]}, {"type": "r", "ref": 3, "children": [{"type": "t", "text": "Linlin Luo, Ruixue Xu, Fuqin Mu, et al. "}, {"type": "b", "children": [{"type": "t", "text": "The interaction between TMEM161B (rs768705) and paranoid personality traits in relation to the risk of major depressive disorder: Results form a longitudinal study of 7642 Chinese freshmen."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "J Affect Disord (2024)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1016/j.jad.2024.08.065"}], "href": "https://doi.org/10.1016/j.jad.2024.08.065"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "39147160"}], "href": "https://pubmed.ncbi.nlm.nih.gov/39147160"}]}, {"type": "r", "ref": 4, "children": [{"type": "t", "text": "Binyin Hou, Lei Ji, Zhixuan Chen, et al. "}, {"type": "b", "children": [{"type": "t", "text": "Role of rs454214 in Personality mediated Depression and Subjective Well-being."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Sci Rep (2020)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1038/s41598-020-62486-x"}], "href": "https://doi.org/10.1038/s41598-020-62486-x"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "32231262"}], "href": "https://pubmed.ncbi.nlm.nih.gov/32231262"}]}, {"type": "r", "ref": 5, "children": [{"type": "t", "text": "Lu Wang, Caleb Heffner, Keng Ioi Vong, et al. "}, {"type": "b", "children": [{"type": "t", "text": "TMEM161B modulates radial glial scaffolding in neocortical development."}]}, {"type": "t", "text": " "}, {"type": "i", "children": [{"type": "t", "text": "Proc Natl Acad Sci U S A (2023)"}]}, {"type": "t", "text": " DOI: "}, {"type": "a", "children": [{"type": "t", "text": "10.1073/pnas.2209983120"}], "href": "https://doi.org/10.1073/pnas.2209983120"}, {"type": "t", "text": " PMID: "}, {"type": "a", "children": [{"type": "t", "text": "36669109"}], "href": "https://pubmed.ncbi.nlm.nih.gov/36669109"}]}]}]}