DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder.
Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders tha...
Guardado en:
| Autores principales: | , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , , |
|---|---|
| Formato: | article |
| Lenguaje: | EN |
| Publicado: |
Public Library of Science (PLoS)
2012
|
| Materias: | |
| Acceso en línea: | https://doaj.org/article/1e9c72c4001d4992b35c0bcc3e363b3c |
| Etiquetas: |
Agregar Etiqueta
Sin Etiquetas, Sea el primero en etiquetar este registro!
|
| id |
oai:doaj.org-article:1e9c72c4001d4992b35c0bcc3e363b3c |
|---|---|
| record_format |
dspace |
| spelling |
oai:doaj.org-article:1e9c72c4001d4992b35c0bcc3e363b3c2021-11-18T07:21:17ZDCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder.1932-620310.1371/journal.pone.0035424https://doaj.org/article/1e9c72c4001d4992b35c0bcc3e363b3c2012-01-01T00:00:00Zhttps://www.ncbi.nlm.nih.gov/pmc/articles/pmid/22539971/pdf/?tool=EBIhttps://doaj.org/toc/1932-6203Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders that have neuro-cognitive dysfunctions: schizophrenia (SCZ), bipolar affective disorder (BP) and attention deficit/hyperactivity disorder (ADHD). We mined six genome wide association studies (GWASs) that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also genotyped the DCLK1 region in additional samples of cases with SCZ, BP or ADHD and controls that had not been whole-genome typed. In total, 9895 subjects were analysed, including 5308 normal controls and 4,587 patients (1,125 with SCZ, 2,496 with BP and 966 with ADHD). Several DCLK1 variants were associated with disease phenotypes in the different samples. The main effect was observed for rs7989807 in intron 3, which was strongly associated with SCZ alone and even more so when cases with SCZ and ADHD were combined (P-value = 4 × 10(-5) and 4 × 10(-6), respectively). Associations were also observed with additional markers in intron 3 (combination of SCZ, ADHD and BP), intron 19 (SCZ+BP) and the 3'UTR (SCZ+BP). Our results suggest that genetic variants in DCLK1 are associated with SCZ and, to a lesser extent, with ADHD and BP. Interestingly the association is strongest when SCZ and ADHD are considered together, suggesting common genetic susceptibility. Given that DCLK1 variants were previously found to be associated with cognitive traits, these results are consistent with the role of DCLK1 in neurodevelopment and synaptic plasticity.Bjarte HåvikFranziska A DegenhardtStefan JohanssonCarla P D FernandesAnke HinneyAndré ScheragHelle LybækSrdjan DjurovicAndrea ChristoforouKari M ErslandSudheer GiddaluruMichael C O'DonovanMichael J OwenNick CraddockThomas W MühleisenManuel MattheisenBenno G SchimmelmannTobias RennerAndreas WarnkeBeate Herpertz-DahlmannJudith SinzigÖzgür AlbayrakMarcella RietschelMarkus M NöthenClive R BramhamThomas WergeJohannes HebebrandJan HaavikOle A AndreassenSven CichonVidar M SteenStéphanie Le HellardPublic Library of Science (PLoS)articleMedicineRScienceQENPLoS ONE, Vol 7, Iss 4, p e35424 (2012) |
| institution |
DOAJ |
| collection |
DOAJ |
| language |
EN |
| topic |
Medicine R Science Q |
| spellingShingle |
Medicine R Science Q Bjarte Håvik Franziska A Degenhardt Stefan Johansson Carla P D Fernandes Anke Hinney André Scherag Helle Lybæk Srdjan Djurovic Andrea Christoforou Kari M Ersland Sudheer Giddaluru Michael C O'Donovan Michael J Owen Nick Craddock Thomas W Mühleisen Manuel Mattheisen Benno G Schimmelmann Tobias Renner Andreas Warnke Beate Herpertz-Dahlmann Judith Sinzig Özgür Albayrak Marcella Rietschel Markus M Nöthen Clive R Bramham Thomas Werge Johannes Hebebrand Jan Haavik Ole A Andreassen Sven Cichon Vidar M Steen Stéphanie Le Hellard DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. |
| description |
Doublecortin and calmodulin like kinase 1 (DCLK1) is implicated in synaptic plasticity and neurodevelopment. Genetic variants in DCLK1 are associated with cognitive traits, specifically verbal memory and general cognition. We investigated the role of DCLK1 variants in three psychiatric disorders that have neuro-cognitive dysfunctions: schizophrenia (SCZ), bipolar affective disorder (BP) and attention deficit/hyperactivity disorder (ADHD). We mined six genome wide association studies (GWASs) that were available publically or through collaboration; three for BP, two for SCZ and one for ADHD. We also genotyped the DCLK1 region in additional samples of cases with SCZ, BP or ADHD and controls that had not been whole-genome typed. In total, 9895 subjects were analysed, including 5308 normal controls and 4,587 patients (1,125 with SCZ, 2,496 with BP and 966 with ADHD). Several DCLK1 variants were associated with disease phenotypes in the different samples. The main effect was observed for rs7989807 in intron 3, which was strongly associated with SCZ alone and even more so when cases with SCZ and ADHD were combined (P-value = 4 × 10(-5) and 4 × 10(-6), respectively). Associations were also observed with additional markers in intron 3 (combination of SCZ, ADHD and BP), intron 19 (SCZ+BP) and the 3'UTR (SCZ+BP). Our results suggest that genetic variants in DCLK1 are associated with SCZ and, to a lesser extent, with ADHD and BP. Interestingly the association is strongest when SCZ and ADHD are considered together, suggesting common genetic susceptibility. Given that DCLK1 variants were previously found to be associated with cognitive traits, these results are consistent with the role of DCLK1 in neurodevelopment and synaptic plasticity. |
| format |
article |
| author |
Bjarte Håvik Franziska A Degenhardt Stefan Johansson Carla P D Fernandes Anke Hinney André Scherag Helle Lybæk Srdjan Djurovic Andrea Christoforou Kari M Ersland Sudheer Giddaluru Michael C O'Donovan Michael J Owen Nick Craddock Thomas W Mühleisen Manuel Mattheisen Benno G Schimmelmann Tobias Renner Andreas Warnke Beate Herpertz-Dahlmann Judith Sinzig Özgür Albayrak Marcella Rietschel Markus M Nöthen Clive R Bramham Thomas Werge Johannes Hebebrand Jan Haavik Ole A Andreassen Sven Cichon Vidar M Steen Stéphanie Le Hellard |
| author_facet |
Bjarte Håvik Franziska A Degenhardt Stefan Johansson Carla P D Fernandes Anke Hinney André Scherag Helle Lybæk Srdjan Djurovic Andrea Christoforou Kari M Ersland Sudheer Giddaluru Michael C O'Donovan Michael J Owen Nick Craddock Thomas W Mühleisen Manuel Mattheisen Benno G Schimmelmann Tobias Renner Andreas Warnke Beate Herpertz-Dahlmann Judith Sinzig Özgür Albayrak Marcella Rietschel Markus M Nöthen Clive R Bramham Thomas Werge Johannes Hebebrand Jan Haavik Ole A Andreassen Sven Cichon Vidar M Steen Stéphanie Le Hellard |
| author_sort |
Bjarte Håvik |
| title |
DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. |
| title_short |
DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. |
| title_full |
DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. |
| title_fullStr |
DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. |
| title_full_unstemmed |
DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. |
| title_sort |
dclk1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder. |
| publisher |
Public Library of Science (PLoS) |
| publishDate |
2012 |
| url |
https://doaj.org/article/1e9c72c4001d4992b35c0bcc3e363b3c |
| work_keys_str_mv |
AT bjartehavik dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT franziskaadegenhardt dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT stefanjohansson dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT carlapdfernandes dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT ankehinney dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT andrescherag dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT hellelybæk dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT srdjandjurovic dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT andreachristoforou dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT karimersland dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT sudheergiddaluru dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT michaelcodonovan dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT michaeljowen dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT nickcraddock dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT thomaswmuhleisen dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT manuelmattheisen dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT bennogschimmelmann dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT tobiasrenner dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT andreaswarnke dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT beateherpertzdahlmann dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT judithsinzig dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT ozguralbayrak dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT marcellarietschel dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT markusmnothen dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT cliverbramham dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT thomaswerge dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT johanneshebebrand dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT janhaavik dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT oleaandreassen dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT svencichon dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT vidarmsteen dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder AT stephanielehellard dclk1variantsareassociatedacrossschizophreniaandattentiondeficithyperactivitydisorder |
| _version_ |
1718423582867980288 |