TY  - JOUR
A1  - Havik, Bjarte
A1  - Degenhardt, Franziska A.
A1  - Johansson, Stefan
A1  - Fernandes, Carla P. D.
A1  - Hinney, Anke
A1  - Scherag, André
A1  - Lybaek, Helle
A1  - Djurovic, Srdjan
A1  - Christoforou, Andrea
A1  - Ersland, Kari M.
A1  - Giddaluru, Sudheer
A1  - O'Donovan, Michael C.
A1  - Owen, Michael J.
A1  - Craddock, Nick
A1  - Mühleisen, Thomas W.
A1  - Mattheisen, Manuel
A1  - Schimmelmann, Benno G.
A1  - Renner, Tobias
A1  - Warnke, Andreas
A1  - Herpertz-Dahlmann, Beate
A1  - Sinzig, Judith
A1  - Albayrak, Özgür
A1  - Rietschel, Marcella
A1  - Nöthen, Markus M.
A1  - Bramham, Clive R.
A1  - Werge, Thomas
A1  - Hebebrand, Johannes
A1  - Haavik, Jan
A1  - Andreassen, Ole A.
A1  - Cichon, Sven
A1  - Steen, Vidar M.
A1  - Le Hellard, Stephanie
T1  - DCLK1 Variants Are Associated across Schizophrenia and Attention Deficit/Hyperactivity Disorder
JF  - PLoS One
N2  - 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 = 4x10\(^{-5}\) and 4x10\(^{-6}\), 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.
KW  - psychosis
KW  - deficit hyperactivity disorder
KW  - genome-wide association
KW  - bipolar disorder
KW  - VAL66MET polymorphism
KW  - doublecortine-like
KW  - genes
KW  - kinase
KW  - BDNF
KW  - endophenotype
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-135285
VL  - 7
IS  - 4
ER  - 
TY  - JOUR
A1  - Brevik, Erlend J
A1  - van Donkelaar, Marjolein M. J.
A1  - Weber, Heike
A1  - Sánchez-Mora, Cristina
A1  - Jacob, Christian
A1  - Rivero, Olga
A1  - Kittel-Schneider, Sarah
A1  - Garcia-martinez, Iris
A1  - Aebi, Marcel
A1  - van Hulzen, Kimm
A1  - Cormand, Bru
A1  - Ramos-Quiroga, Josep A
A1  - Lesch, Klaus-Peter
A1  - Reif, Andreas
A1  - Ribases, Marta
A1  - Franke, Barbara
A1  - Posserud, Maj-Britt
A1  - Johansson, Stefan
A1  - Lundervold, Astri J.
A1  - Haavik, Jan
A1  - Zayats, Tetyana
T1  - Genome-wide analyses of aggressiveness in attention-deficit hyperactivity disorder
JF  - American Journal of Medical Genetics Part B-Neuropsychiatric Genetics
N2  - Aggressiveness is a behavioral trait that has the potential to be harmful to individuals and society. With an estimated heritability of about 40%, genetics is important in its development. We performed an exploratory genome-wide association (GWA) analysis of childhood aggressiveness in attention deficit hyperactivity disorder (ADHD) to gain insight into the underlying biological processes associated with this trait. Our primary sample consisted of 1,060 adult ADHD patients (aADHD). To further explore the genetic architecture of childhood aggressiveness, we performed enrichment analyses of suggestive genome-wide associations observed in aADHD among GWA signals of dimensions of oppositionality (defiant/vindictive and irritable dimensions) in childhood ADHD (cADHD). No single polymorphism reached genome-wide significance (P<5.00E-08). The strongest signal in aADHD was observed at rs10826548, within a long noncoding RNA gene (beta = -1.66, standard error (SE) = 0.34, P = 1.07E-06), closely followed by rs35974940 in the neurotrimin gene (beta = 3.23, SE = 0.67, P = 1.26E-06). The top GWA SNPs observed in aADHD showed significant enrichment of signals from both the defiant/vindictive dimension (Fisher's P-value = 2.28E-06) and the irritable dimension in cADHD (Fisher's P-value = 0.0061). In sum, our results identify a number of biologically interesting markers possibly underlying childhood aggressiveness and provide targets for further genetic exploration of aggressiveness across psychiatric disorders.
KW  - Large multicenter ADHD
KW  - Antisocial behavior
KW  - Diagnostic approach
KW  - Rating scale
KW  - Gene
KW  - Deficit/hyperactivity disorder
KW  - Susceptibility loci
KW  - Conduct disorder
KW  - Association
KW  - Adult
KW  - ADHD
KW  - Aggression
KW  - GWAS
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-188116
VL  - 171B
IS  - 5
ER  -