Erratum: Genome-wide association study of obsessive-compulsive disorder

Stewart, S. Evelyn; Yu, Dongmei; Scharf, Jeremiah M.; Neale, B. M.; Fagerness, Jes; Mathews, Carol A.; Arnold, Petra; Evans, Patrick; Gamazon, Eric R.; Osiecki, Lisa; McGrath, Lauren M.; Haddad, Sana; Crane, John S.; Hezel, Dianne M.; Illman, C; Mayerfeld, C.; Konkashbaev, Anuar; Liu, C; Pluzhnikov, Anna; Тихомиров, А. А.; Edlund, Christopher K.; Rauch, S.L.; Moessner, Rainald; Falkai, Peter; Maier, Wolfgang; Ruhrmann, S; Grabe, HJ; Lennertz, Leonhard; Wagner, Michael; Bellodi, Laura; Cavallini, Maria Cristina; Richter, Margaret A.; Cook, Edwin H.; Kennedy, James L.; Rosenberg, David; Stein, Dan J.; Hemmings, Sı̂an M.J.; Löchner, Christine; Azzam, Amin; Chavira, Denise A.; Fournier, E; Garrido, Helena; Sheppard, Brooke; Umaña, Paula; Murphy, Dennis L.; Wendland, Jens R.; Weele, Jeremy Veenstra-Vander; Denys, Damiaan; Blom, Rianne M.; Deforce, Dieter; Nieuwerburgh, Filip Van; Westenberg, H. G. M.; Walitza, Susanne; Egberts, Karin; Renner, Tobias; Miguel, Euripides C.; Cappi, Carolina; Hounie, Ana Gabriela; Rosário, Maria Conceição do; Sampaio, Aline Santos; Vallada, Homero; Nicolini, Humberto; Lanzagorta, Nuria; Camarena, Beatríz; Delorme, Richard; Leboyer, Marion; Pato, C.N.; Pato, Michele T.; Voyiaziakis, Emanuel; Heutink, Peter; Cath, D.C.; Posthuma, Daniëlle; Smit, JH; Samuels, Jack; Bienvenu, O. Joseph; Cullen, Bernadette; Fyer, Abby J.; Grados, Marco A.; Greenberg, Benjamim D; McCracken, James T.; Riddle, Mark A.; Wang, Y; Coric, Vladimir; Leckman, James F.; Bloch, Michael H.; Pittenger, Christopher; Eapen, Valsamma; Black, Dora; Ophoff, R. A.; Strengman, Eric; Cusi, D.; Turiel, M.; Frau, Francesca; Macciardi, Fabìo; Gibbs, J. Raphael; Cookson, Mark; Singleton, A; Hardy, John; Crenshaw, Andrew; Parkin, Melissa; Mirel, Daniel B.; Conti, DV; Purcell, Shaun; Nestadt, Gerald; Hanna, Gregory L.; Jenike, Michael A.; Knowles, James A.; Cox, Nancy J.; Pauls, David L.

doi:10.1038/mp.2013.15

Cited by 3 publications

(2 citation statements)

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“…T A B L E 2 Significant cis-MeQTLs and mediation results 42 which may play a role in the cognitive and social deficits seen in some psychiatric disorders. 43,44 While our replicating finding was in blood, the same site was not significant in both the mCG and hmCG data in brain and was not associated with DLGAP1 expression levels. However, there were two mCG sites in DLGAP1 in our brain MWAS that were nominally significant and among the cross-tissue overlap.…”

Section: Replication Of Existing Mcg Findingsmentioning

confidence: 44%

Dual methylation and hydroxymethylation study of alcohol use disorder

et al. 2021

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Using an integrative, multi-tissue design, we sought to characterize methylation and hydroxymethylation changes in blood and brain associated with alcohol use disorder (AUD). First, we used epigenomic deconvolution to perform cell-type-specific methylome-wide association studies within subpopulations of granulocytes/T-cells/ B-cells/monocytes in 1132 blood samples. Blood findings were then examined for overlap with AUD-related associations with methylation and hydroxymethylation in 50 human post-mortem brain samples. Follow-up analyses investigated if overlapping findings mediated AUD-associated transcription changes in the same brain samples. Lastly, we replicated our blood findings in an independent sample of 412 individuals and aimed to replicate published alcohol methylation findings using our results. Celltype-specific analyses in blood identified methylome-wide significant associations in monocytes and T-cells. The monocyte findings were significantly enriched for AUD-

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Section: Replication Of Existing Mcg Findingsmentioning

confidence: 44%

Dual methylation and hydroxymethylation study of alcohol use disorder

et al. 2021

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“…A meta-analysis of genetic polymorphisms previously implicated in OCD suggested a role of serotonergic genes (the serotonin transporter SLC6A4 and the serotonin 2A receptor HTR2A) in OCD vulnerability [18]. On the other hand, recent genome-wide association studies (GWAS) have not identified involvement of serotonergic genes at genome-wide significant levels [19,20]. However, in a GWAS investigating genetic polymorphisms influencing treatment response to SRIs in OCD, enrichment analysis suggested a role for serotonergic and glutamatergic genes polymorphisms [21].…”

Section: Dysregulation Of Neurotransmitter Signalling In Ocdmentioning

confidence: 99%

Glutamate-modulating drugs as a potential therapeutic strategy in obsessive-compulsive disorder

Marinova¹

2016

Preprint

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Objective: Obsessive-compulsive disorder (OCD) is a mental disease commonly associated with severe distress and impairment of social functioning. Serotonin reuptake inhibitors and/or cognitive behavioural therapy are the therapy of choice, however up to 40% of patients do not respond to treatment. Glutamatergic signalling has also been implicated in OCD. The aim of the current study was to review the clinical evidence for therapeutic utility of glutamate-modulating drugs as an augmentation or monotherapy in OCD patients. Methods: We conducted a search of the MEDLINE database for clinical studies evaluating the effect of glutamate-modulating drugs in OCD. Results: Memantine is the compound most consistently showing a positive effect as an augmentation therapy in OCD. Anti-convulsant drugs (lamotrigine, topiramate) and riluzole may also provide therapeutic benefit to some OCD patients. Finally, ketamine may be of interest due to its potential for a rapid onset of action. Conclusion: Further randomized placebo-controlled trials in larger study populations are necessary in order to draw definitive conclusions on the utility of glutamate-modulating drugs in OCD. Furthermore, genetic and epigenetic factors, clinical symptoms and subtypes predicting treatment response to glutamate-modulating drugs need to be investigated systematically.

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Late development of OCD-like phenotypes in Dlgap1 knockout mice

Minagawa,

Hayakawa,

Akimoto

et al. 2024

Psychopharmacology

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Rationale Despite variants in the Dlgap1 gene having the two lowest p-value in a genome-wide association study of obsessive compulsive disorder (OCD), previous studies reported the absence of OCD-like phenotypes in Dlgap1 knockout (KO) mice. Since these studies observed behavioral phenotypes only for a short period, development of OCD-like phenotypes in these mice at older ages was still plausible. Objective To examine the presence or absence of development of OCD-like phenotypes in Dlgap1 KO mice and their responsiveness to fluvoxamine. Methods and results Newly produced Dlgap1 KO mice were observed for a year. Modified SHIRPA primary screen in 2-month-old homozygous mutant mice showed only weak signs of anxiety, stress conditions and aggression. At older ages, however, these mutant mice exhibited excessive self-grooming characterized by increased scratching which led to skin lesions. A significant sex difference was observed in this scratching behavior. The penetrance of skin lesions reached 50% at 6–7 months of age and 90% at 12 months of age. In the open-field test performed just after the appearance of these lesions, homozygous mutant mice spent significantly less time in the center, an anxiety-like behavior, than did their wild-type and heterozygous littermates, none and less than 10% of which showed skin lesions at 1 year, respectively. The skin lesions and excessive self-grooming were significantly alleviated by two-week treatment with fluvoxamine. Conclusion Usefulness of Dlgap1 KO mice as a tool for investigating the pathogenesis of OCD-like phenotypes and its translational relevance was suggested.

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Erratum: Genome-wide association study of obsessive-compulsive disorder

Cited by 3 publications

References 0 publications

Dual methylation and hydroxymethylation study of alcohol use disorder

Dual methylation and hydroxymethylation study of alcohol use disorder

Glutamate-modulating drugs as a potential therapeutic strategy in obsessive-compulsive disorder

Late development of OCD-like phenotypes in Dlgap1 knockout mice

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