ADHDgene Database

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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

Detail ...

Study Report

Basic Info

Reference	Jarick, I., 201223164820
Citation	Jarick I., Volckmar A. L., Putter C., Pechlivanis S., Nguyen T. T., Dauvermann M. R., Beck S., Albayrak O., Scherag S., Gilsbach S., Cichon S., Hoffmann P., Degenhardt F., Nothen M. M., Schreiber S., Wichmann H. E., Jockel K. H., Heinrich J., Tiesler C. M., Faraone S. V., Walitza S., Sinzig J., Freitag C., Meyer J., Herpertz-Dahlmann B., Lehmkuhl G., Renner T. J., Warnke A., Romanos M., Lesch K. P., Reif A., Schimmelmann B. G., Hebebrand J., Scherag A. and Hinney A. (2012) "Genome-wide analysis of rare copy number variations reveals PARK2 as a candidate gene for attention-deficit/hyperactivity disorder." Mol Psychiatry.
Study Design	case-control
Study Type	Genome-wide CNV analysis
Sample Size	489 cases and 1285 controls
Predominant Ethnicity	Caucasian
Population	German
Gender	GWAS ADHD cases: 396 males (81%), 93 females (19%)
Age Group	Children/Adolescents : age range: 6-18 years, mean age: 11.0 years(SD=2.7)

Detail Info

Summary	To identify rare (frequency <=1%) CNVs that increase the risk of ADHD, we performed a whole-genome CNV analysis based on 489 young ADHD patients and 1285 adult population-based controls and identified one significantly associated CNV region. In tests for a global burden of large (>500 kb) rare CNVs, we observed a nonsignificant (P=0.271) 1.126-fold enriched rate of subjects carrying at least one such CNV in the group of ADHD cases. Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls. We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8E-4 after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6:162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2E-3 after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3E-2). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.
Total Sample	A whole-genome CNV analysis was performed based on 489 young ADHD patients and 1285 adult population-based controls. Findings were replicated in an independent sample of 386 young patients with ADHD and 781 young population-based healthy controls.
Replication Size	386 cases and 781 controls
Sample Collection	The GWAS cases are all German minors with ADHD, recruited and phenotypically characterized in six psychiatric outpatient units for children and adolescents (Aachen, Cologne, Essen, Marburg, Regensburg and Wurzburg). In addition, controls were drawn from three German population-based epidemiological studies in adults for the GWAS step: (a) the Heinz Nixdorf RECALL (Risk Factors, Evaluation of Coronary Calcification, and Lifestyle) study (HNR, n=383), (b) PopGen (n=490) and (c) KORA (n=488). The recruitment areas were Essen, Bochum and Mulheim (Ruhr area) for (a), Schleswig-Holstein (Northern Germany) for (b) and Augsburg (Southern Germany) for (c), respectively. Compared with the ADHD cases, the population-based controls were less frequently male (cases: 81.0% male; controls: 50.7% male) and older (age range cases: 6¨C18 years; age range controls: 25¨C75 years). The case group of the replication sample were recruited and phenotypically characterized in two outpatient clinics at the Departments of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy of the Universities of Homburg and Wurzburg, Germany.
Diagnosis Description	In total, 504 patients recruited for the GWAS step were assessed for the diagnosis ADHD according to DSM-IV.
Technique	Locus-specific tests of association were used to assess if there were more rare CNVs in cases compared with controls. Detected CNVs, which were significantly enriched in the ADHD group, were validated by quantitative (q)PCR.
Analysis Method	All association analyses were performed on the QC filtered, rare CNV calls were investigated using the PLINK software (version 1.07). Locus-specific tests of association were performed (one-sided chi-square tests) and significance was assessed via permutation (empirical P-values based on 100,000 permutations) at a pointwise as well as at a genome-wide level. The frequency of rare CNVs in ADHD patients was calculated, and it was compared to the frequency in the controls. The frequency was calculated at each unique start and stop site for rare CNVs. Each site was assessed for a difference in CNV frequency between groups with the use of a permutation-based Fisher's exact test in PLINK. As secondary sensitivity analyses, the genome-wide frequency of CNVs was also assessed in ADHD cases compared with controls according to the average number of CNVs per sample. Finally, they tested whether CNVs in the ADHD cases were larger in size than those in the control group based on the average size of CNVs per individual.
Result Description	We identified rare CNVs within the parkinson protein 2 gene (PARK2) with a significantly higher prevalence in ADHD patients than in controls (P=2.8E-4 after empirical correction for genome-wide testing). In total, the PARK2 locus (chr 6:162 659 756-162 767 019) harboured three deletions and nine duplications in the ADHD patients and two deletions and two duplications in the controls. By qPCR analysis, we validated 11 of the 12 CNVs in ADHD patients (P=1.2E-3 after empirical correction for genome-wide testing). In the replication sample, CNVs at the PARK2 locus were found in four additional ADHD patients and one additional control (P=4.3E-2). Our results suggest that copy number variants at the PARK2 locus contribute to the genetic susceptibility of ADHD. Mutations and CNVs in PARK2 are known to be associated with Parkinson disease.

CNVs reported by this study (count: 50)

Name	Symbol in Literature	Type	Author Comments
CNV_Jarick[2012]_2	chr1:144943150-146293282	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_1	chr1:109103606-109682244	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_4	chr2:78445675-79752445	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_3	chr2:13708699-14257740	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_28	chr13:85838283-86606426	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_27	chr12:128372933-129048936	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_26	chr12:122465458-124605386	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_25	chr12:33415349-34692538	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_24	chr11:50021328-50669978	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_23	chr10:132453545-135284293	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_22	chr10:52492354-53412126	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_21	chr10:19425254-20059857	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_36	chr16:82208011-82797605	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_35	chr16:29554843-30085308	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_34	chr16:17403825-18174650	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_33	chr16:15387380-16197033	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_32	chr16:15034391-16197033	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_31	chr16:15032942-16197033	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_30	chr15:28797383-30302218	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_29	chr15:27216380-28153539	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_11	chr4:116331940-117593576	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_12	chr4:167382752-168375955	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_9	chr3:176569238-177225442	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_10	chr4:29765561-30996622	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_7	chr3:653347-1551741	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_8	chr3:140757013-141415656	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_5	chr2:131198948-131951456	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_6	chr3:38411-1102372	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_19	chr7:124764972-125581531	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_20	chr9:106634185-107206459	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_17	chr7:61681059-62336389	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_18	chr7:105951552-106708212	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_15	chr6:141179444-142373774	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_16	chr7:61681059-62342453	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_13	chr5:155472889-156309281	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_14	chr5:178157153-180497731	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_41	chr22:17616020-19792353	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_42	chr22:19066315-19792353	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_43	chr6:162477709-162724935	del	Rare CNVs identified in ADHD cases at the PARK2 locus which ...... Rare CNVs identified in ADHD cases at the PARK2 locus which were validated by qPCR experiments More...
CNV_Jarick[2012]_44	chr6:162629938-162935269	dup	Rare CNVs identified in ADHD cases at the PARK2 locus which ...... Rare CNVs identified in ADHD cases at the PARK2 locus which were validated by qPCR experiments More...
CNV_Jarick[2012]_37	chr16:82878275-83630163	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_38	chr17:69439887-70135450	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_39	chr18:61970295-64368411	del	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_40	chr22:17257787-19792353	dup	Rare CNV larger than 500 kb identified in the GWAS ADHD case...... Rare CNV larger than 500 kb identified in the GWAS ADHD cases More...
CNV_Jarick[2012]_49	chr6:162687672-162789187	del	Rare CNVs identified in ADHD cases at the PARK2 locus which ...... Rare CNVs identified in ADHD cases at the PARK2 locus which were validated by qPCR experiments More...
CNV_Jarick[2012]_50	chr6:162687672-162896029	del	Rare CNVs identified in ADHD cases at the PARK2 locus which ...... Rare CNVs identified in ADHD cases at the PARK2 locus which were validated by qPCR experiments More...
CNV_Jarick[2012]_45	chr6:162637688-162809965	dup	Rare CNVs identified in ADHD cases at the PARK2 locus which ...... Rare CNVs identified in ADHD cases at the PARK2 locus which were validated by qPCR experiments More...
CNV_Jarick[2012]_46	chr6:162644237-162829925	dup	Rare CNVs identified in ADHD cases at the PARK2 locus which ...... Rare CNVs identified in ADHD cases at the PARK2 locus which were validated by qPCR experiments More...
CNV_Jarick[2012]_47	chr6:162644237-162834976	dup	Rare CNVs identified in ADHD cases at the PARK2 locus which ...... Rare CNVs identified in ADHD cases at the PARK2 locus which were validated by qPCR experiments More...
CNV_Jarick[2012]_48	chr6:162674596-162834976	dup	Rare CNVs identified in ADHD cases at the PARK2 locus which ...... Rare CNVs identified in ADHD cases at the PARK2 locus which were validated by qPCR experiments More...

Genes reported by this study (count: 1)