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

Study Report

Basic Info

Reference	Romanos M, 200818301393
Citation	Romanos M., Freitag C., Jacob C., Craig D. W., Dempfle A., Nguyen T. T., Halperin R., Walitza S., Renner T. J., Seitz C., Romanos J., Palmason H., Reif A., Heine M., Windemuth-Kieselbach C., Vogler C., Sigmund J., Warnke A., Schafer H., Meyer J., Stephan D. A. and Lesch K. P. (2008) "Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13.1 and 14q12." Mol Psychiatry, 13(5): 522-30.
Study Design	pedigree
Study Type	Genome-wide linkage study
Sample Size	8 families, 191 individuals
Predominant Ethnicity	Caucasian
Population	Germany
Age Group	Children/Adolescents and Adults

Detail Info

Summary	They investigated eight extended pedigrees of German origin that were non-related, not part of a genetic isolate and ascertained on the basis of clinical referral. Two parametric analyses maximizing LOD scores (MOD) and a non-parametric analysis for both a broad and a narrow phenotype approach were conducted. Novel linkage loci across all families were detected at 2q35, 5q13.1, 6q22-23 and 14q12, within individual families at 18q11.2-12.3. Further linkage regions at 7q21.11, 9q22 and 16q24.1 in all families, and at 1q25.1, 1q25.3, 9q31.1-33.1, 9q33, 12p13.33, 15q11.2-13.3 and 16p12.3-12.2 in individual families replicate previous findings. High-resolution linkage mapping points to several novel candidate genes characterized by dense expression in the brain and potential impact on disorder-relevant synaptic transmission. Their study provides further evidence for common gene effects throughout different populations despite the complex multifactorial etiology of ADHD.
Total Sample	They ascertained families of German origin through index children referred to three outpatient clinics in Wuerzburg, Homburg or Trier. The structure of the eight families (Pedigree 1-8; P1-P8) is shown in the original publication.
Sample Collection	German origin
Diagnosis Description	Children and adolescents were clinically characterized by a semi-structured interview, child behavior checklist and by an ADHD diagnostic checklist applying DSM-IV criteria categorically and dimensionally. Teacher ratings were obtained. Adult participants were also rated by the SDS and the ADHD-DC, based on a semi-structured interview, thus enabling transgenerational comparability of current ADHD affection. Current and retrospective self-ratings were obtained. Symptoms were assessed by the Wender Utah Rating Scale, retrospectively. In families recruited in Homburg and Trier, additionally the Wender Reimherr Interview was used.
Technique	Genomic DNA was extracted from blood samples according to standard protocols. DNA samples were diluted to a concentration of 50 ng ul-1 suspended in TE-buffer. For genotyping of ~50,000 SNPs, the GeneChip Human Mapping 50K Array Hind240 (dBSNP build 125) was used according to the recommendations of Affymetrix.
Analysis Method	Two parametric analyses maximizing LOD scores (MOD) and a non-parametric analysis for both a broad and a narrow phenotype approach were conducted.
Result Description	Novel linkage loci across all families were detected at 2q35, 5q13.1, 6q22-23 and 14q12, within individual families at 18q11.2-12.3. Further linkage regions at 7q21.11, 9q22 and 16q24.1 in all families, and at 1q25.1, 1q25.3, 9q31.1-33.1, 9q33, 12p13.33, 15q11.2-13.3 and 16p12.3-12.2 in individual families replicate previous findings. The study provides further evidence for common gene effects throughout different populations despite the complex multifactorial etiology of ADHD.

Regions reported by this study (count: 15)

Region	Statistical Values	Author Comments	Result of Statistical Analysis
2q35	MODglobal=2.98, MODsingle=3.4, NPL=2.32 for the narrow phenotype; MODglobal=1.2, MODsingle=1.26, NPL=2.26 for the broad phenotype in P1,2,3,8	linkage across all families was detected linkage across all families was detected	Significant
5q13.1	MODglobal=2.82, MODsingle=2.82, NPL=2.96 for the narrow phenotype; MODglobal=4.16, MODsingle=4.08, NPL=2.49 for the broad phenotype in P1,3,8	linkage across all families was detected linkage across all families was detected	Significant
6q22-23	MODglobal=2.75, MODsingle=3.32, NPL=1.78 for the narrow phenotype; MODglobal=1.44, MODsingle=1.63, NPL=1.47 for the broad phenotype in P1,3,5,6,7,8	linkage across all families was detected linkage across all families was detected	Significant
7q21.11	MODglobal=3.14, MODsingle=3.14, NPL=1.37 for the narrow phenotype; MODglobal=2.18, MODsingle=2.19, NPL=1.26 for the broad phenotype in P1,2,3,5,6,7,8	linkage across all families was detected linkage across all families was detected	Trend
9q22	MODglobal=1.39, MODsingle=1.94, NPL=3.1 for the narrow phenotype; MODglobal=3.3, MODsingle=3.07, NPL=2.09 for the broad phenotype in P1,3,4,5,6,7,8	linkage across all families was detected linkage across all families was detected	Significant
14q12	MODglobal=4.17, MODsingle=4.5, NPL=2.07 for the narrow phenotype; MODglobal=2.99, MODsingle=2.77, NPL=2 for the broad phenotype in P1,2,3,4,7,8	linkage across all families was detected linkage across all families was detected	Significant
16q24.1	MODglobal=3.26, MODsingle=3.2, NPL=3.57 for the narrow phenotype; MODglobal=1.88, MODsingle=2.03, NPL=3.86 for the broad phenotype in P2,3,5,7,8	linkage across all families was detected linkage across all families was detected	Trend
1q25.1	MODglobal=4.17, MODsingle=4.17, NPL=7.34 for the narrow phenotype; MODglobal=1.79, MODsingle=1.79, NPL=4.33 for the broad phenotype in P2	linkage in individual families was identified linkage in individual families was identified	Significant
1q25.3	MODglobal=2.99, MODsingle=2.99, NPL=6 for the narrow phenotype; MODglobal=0.85, MODsingle=0.91, NPL=0.68 for the broad phenotype in P8	linkage in individual families was identified linkage in individual families was identified	Significant
9q31.1-33.1	MODglobal=1.5, MODsingle=1.5, NPL=3.2 for the narrow phenotype; MODglobal=2.59, MODsingle=2.59, NPL=9.51 for the broad phenotype in P1	linkage in individual families was identified linkage in individual families was identified	Significant
9q33	MODglobal=2.52, MODsingle=2.52, NPL=5.67 for the narrow phenotype; MODglobal=1.91, MODsingle=1.91, NPL=3.41 for the broad phenotype in P5	linkage in individual families was identified linkage in individual families was identified	Significant
12p13.33	MODglobal=3.11, MODsingle=3.11, NPL=5.12 for the narrow phenotype; MODglobal=2.32, MODsingle=2.32, NPL=5.28 for the broad phenotype in P2	linkage in individual families was identified linkage in individual families was identified	Trend
15q11.2-13.3	MODglobal=3.68, MODsingle=3.68, NPL=4.68 for the narrow phenotype; MODglobal=1.97, MODsingle=1.97, NPL=1.84 for the broad phenotype in P2	linkage in individual families was identified linkage in individual families was identified	Significant
18q11.2-12.3	MODglobal=2.9, MODsingle=2.9, NPL=5.31 for the narrow phenotype; MODglobal=1.82, MODsingle=1.82, NPL=4.09 for the broad phenotype in P2	linkage in individual families was identified linkage in individual families was identified	Significant
16p12.3-12.2	MODglobal=1.41, MODsingle=2.11, NPL=1.69 for the narrow phenotype; MODglobal=3.84, MODsingle=3.84, NPL=4.47 for the broad phenotype in P1	linkage in individual families was identified linkage in individual families was identified	Significant