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Large-scale studies

Data Summary

Published Variant
- SNP: 1391
- CNV: 398
- Others: 173
Published Gene: 359
Published Region: 128
Pathway by PBA: 8
Study: 361

Study Report

Basic Info

Reference	Havik, B., 201222539971
Citation	Havik B., Degenhardt F. A., Johansson S., Fernandes C. P., Hinney A., Scherag A., Lybaek H., Djurovic S., Christoforou A., Ersland K. M., Giddaluru S., O'Donovan M. C., Owen M. J., Craddock N., Muhleisen T. W., Mattheisen M., Schimmelmann B. G., Renner T., Warnke A., Herpertz-Dahlmann B., Sinzig J., Albayrak O., Rietschel M., Nothen M. M., Bramham C. R., Werge T., Hebebrand J., Haavik J., Andreassen O. A., Cichon S., Steen V. M. and Le Hellard S. (2012) "DCLK1 variants are associated across schizophrenia and attention deficit/hyperactivity disorder." PLoS One, 7(4): e35424.
Study Design	case-control
Study Type	Candidate-gene association study
Sample Size	466 Norwegian cases and 515 controls; 495 young patients with ADHD and 1300 controls
Predominant Ethnicity	Caucasian
Population	Norwegian and German

Detail Info

Summary	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 x 10(-5) and 4 x 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.
Total Sample	A sample of 466 Norwegian cases and 515 controls was genotyped for markers covering the DCLK1 gene. Later, we extracted genotypes from a GWAS of a sample of cases with ADHD and 1300 controls. This sample consists of 495 young patients with ADHD that were recruited and phenotypically characterized in 8 psychiatric outpatient units in Germany for children and adolescents (Aachen, Cologne, Essen, Marburg, Homburg, Trier, Regensburg, and Wurzburg). Patients were included if they were diagnosed with ADHD according to DSM-IV.
Sample Collection	A sample of 466 Norwegian cases and 515 controls was genotyped for markers covering the DCLK1 gene. Later, we extracted genotypes from a GWAS of a sample of cases with ADHD and 1300 controls. This sample consists of 495 young patients with ADHD that were recruited and phenotypically characterized in 8 psychiatric outpatient units in Germany for children and adolescents (Aachen, Cologne, Essen, Marburg, Homburg, Trier, Regensburg, and Wurzburg).
Diagnosis Description	Norwegian sample: not mentioned. German sample: patients were included if they were diagnosed with ADHD according to DSM-IV. The ascertainment strategy and inclusion criteria have been described previously.
Technique	genotyping: Sequenom Massarray and Illumina 660
Analysis Method	The associations were tested using a logistic regression. The cross-phenotype analyses were performed using a genotypic logistic regression on an additive model using sex and age as covariates. In addition, in order to control for possible confounding effects of geographical location or genotyping platform we included a correction factor which combines both the origin and platform effects. All P-values reported in this study are un-corrected and declared significant at a nominal threshold of P= 0.05. As a guideline to significance, we calculated a Nyholt's SNPSpD gene-based correction.
Result Description	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 x 10(-5) and 4 x 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.

SNPs reported by this study (count: 12)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs10492555			P-value=0.168, OR (95% CI)=1.20 (0.94-1.52) in the Norwegian sample; P-value=0.766, OR (95% CI)=1.05 (0.86-1.29) in the German sample; P-value=0.147, OR (95% CI)=1.15 (0.98-1.33) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs7999483			P-value=0.189, OR (95% CI)=0.82 (0.62-1.09) in the Norwegian sample; P-value=0.287, OR (95% CI)=1.20 (0.96-1.51) in the German sample; P-value=0.809, OR (95% CI)=1.03 (0.87-1.23) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs9545424			P-value=0.055, OR (95% CI)=0.75 (0.57-1.00) in the Norwegian sample; P-value=0.134, OR (95% CI)=1.26 (1.02-1.55) in the German sample; P-value=0.798, OR (95% CI)=1.01 (0.86-1.20) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs9545297			P-value=0.379, OR (95% CI)=0.88 (0.67-1.14) in the Norwegian sample; P-value=0.185, OR (95% CI)=1.20 (0.98-1.47) in the German sample; P-value=0.521, OR (95% CI)=1.04 (0.89¨C1.22) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs1750921			P-value=0.31, OR (95% CI)=1.11 (0.91-1.37) in the Norwegian sample; P-value=0.422, OR (95% CI)=0.91 (0.77-1.08) in the German sample; P-value=0.982, OR (95% CI)=0.99 (0.87-1.12) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs2051090			P-value=0.991, OR (95% CI)=0.99 (0.83-1.18) in the Norwegian sample; P-value=0.556, OR (95% CI)=1.01 (0.87-1.17) in the German sample; P-value=0.848, OR (95% CI)=1.03 (0.92-1.15) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs10507435			P-value=0.542, OR (95% CI)=0.90 (0.72-1.12) in the Norwegian sample; P-value=0.077, OR (95% CI)=0.86 (0.73-1.02) in the German sample; P-value=0.036, OR (95% CI)=0.84 (0.74-0.96) in the merged sample	The marker showed significant association with ADHD. The marker showed significant association with ADHD.	Significant
rs1926452			P-value=0.786, OR (95% CI)=1.01 (0.78-1.30) in the Norwegian sample; P-value=0.276, OR (95% CI)=0.88 (0.72-1.09) in the German sample; P-value=0.365, OR (95% CI)=0.92 (0.79-1.07) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs7989807			P-value=0.098, OR (95% CI)=1.24 (0.96-1.61) in the Norwegian sample; P-value=0.085, OR (95% CI)=1.22 (0.97-1.53) in the German sample; P-value=0.016, OR (95% CI)=1.29 (1.09-1.53) in the merged sample	The marker showed significant association with ADHD. The marker showed significant association with ADHD.	Significant
rs7327771			P-value=0.497, OR (95% CI)=1.13 (0.80-1.60) in the Norwegian sample; P-value=0.201, OR (95% CI)=1.19 (0.88-1.62) in the German sample; P-value=0.165, OR (95% CI)=1.21 (0.97-1.52) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs7990263			P-value=0.107, OR (95% CI)=0.85 (0.70-1.03) in the Norwegian sample; P-value=0.714, OR (95% CI)=1.02 (0.88-1.20) in the German sample; P-value=0.481, OR (95% CI)=0.93 (0.83-1.05) in the merged sample	The marker did not show significant association with ADHD. The marker did not show significant association with ADHD.	Non-significant
rs12874830			P-value=0.283, OR (95% CI)=1.13 (0.90-1.42) in the Norwegian sample; P-value=0.00022, OR (95% CI)=1.38 (1.16-1.65) in the German sample; P-value=0.00029, OR (95% CI)=1.25 (1.09-1.44) in the merged sample	The marker showed significant association with ADHD. The marker showed significant association with ADHD.	Significant

Genes reported by this study (count: 1)