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  - 
TY  - JOUR
A1  - Zayats, T
A1  - Jacobsen, KK
A1  - Kleppe, R
A1  - Jacob, CP
A1  - Kittel-Schneider, S
A1  - Ribasés, M
A1  - Ramos-Quiroga, JA
A1  - Richarte, V
A1  - Casas, M
A1  - Mota, NR
A1  - Grevet, EH
A1  - Klein, M
A1  - Corominas, J
A1  - Bralten, J
A1  - Galesloot, T
A1  - Vasquez, AA
A1  - Herms, S
A1  - Forstner, AJ
A1  - Larsson, H
A1  - Breen, G
A1  - Asherson, P
A1  - Gross-Lesch, S
A1  - Lesch, KP
A1  - Cichon, S
A1  - Gabrielsen, MB
A1  - Holmen, OL
A1  - Bau, CHD
A1  - Buitelaar, J
A1  - Kiemeney, L
A1  - Faraone, SV
A1  - Cormand, B
A1  - Franke, B
A1  - Reif, A
A1  - Haavik, J
A1  - Johansson, S
T1  - Exome chip analyses in adult attention deficit hyperactivity disorder
JF  - Translational Psychiatry
N2  - Attention-deficit/hyperactivity disorder (ADHD) is a highly heritable childhood-onset neuropsychiatric condition, often persisting into adulthood. The genetic architecture of ADHD, particularly in adults, is largely unknown. We performed an exome-wide scan of adult ADHD using the Illumina Human Exome Bead Chip, which interrogates over 250 000 common and rare variants. Participants were recruited by the International Multicenter persistent ADHD CollaboraTion (IMpACT). Statistical analyses were divided into 3 steps: (1) gene-level analysis of rare variants (minor allele frequency (MAF)<1%); (2) single marker association tests of common variants (MAF⩾1%), with replication of the top signals; and (3) pathway analyses. In total, 9365 individuals (1846 cases and 7519 controls) were examined. Replication of the most associated common variants was attempted in 9847 individuals (2077 cases and 7770 controls) using fixed-effects inverse variance meta-analysis. With a Bonferroni-corrected significance level of 1.82E−06, our analyses of rare coding variants revealed four study-wide significant loci: 6q22.1 locus (P=4.46E−08), where NT5DC1 and COL10A1 reside; the SEC23IP locus (P=6.47E−07); the PSD locus (P=7.58E−08) and ZCCHC4 locus (P=1.79E−06). No genome-wide significant association was observed among the common variants. The strongest signal was noted at rs9325032 in PPP2R2B (odds ratio=0.81, P=1.61E−05). Taken together, our data add to the growing evidence of general signal transduction molecules (NT5DC1, PSD, SEC23IP and ZCCHC4) having an important role in the etiology of ADHD. Although the biological implications of these findings need to be further explored, they highlight the possible role of cellular communication as a potential core component in the development of both adult and childhood forms of ADHD.
KW  - chip analyses
KW  - ADHD
KW  - adulthood
KW  - Illumina Human Exome Bead Chip
Y1  - 2016
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-168297
VL  - 6
IS  - e923
ER  -