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

Meta-analysis Report

Basic Info

Reference	Zhou K, 200818988193
Citation	Zhou K., Dempfle A., Arcos-Burgos M., Bakker S. C., Banaschewski T., Biederman J., Buitelaar J., Castellanos F. X., Doyle A., Ebstein R. P., Ekholm J., Forabosco P., Franke B., Freitag C., Friedel S., Gill M., Hebebrand J., Hinney A., Jacob C., Lesch K. P., Loo S. K., Lopera F., McCracken J. T., McGough J. J., Meyer J., Mick E., Miranda A., Muenke M., Mulas F., Nelson S. F., Nguyen T. T., Oades R. D., Ogdie M. N., Palacio J. D., Pineda D., Reif A., Renner T. J., Roeyers H., Romanos M., Rothenberger A., Schafer H., Sergeant J., Sinke R. J., Smalley S. L., Sonuga-Barke E., Steinhausen H. C., van der Meulen E., Walitza S., Warnke A., Lewis C. M., Faraone S. V. and Asherson P. (2008) "Meta-analysis of genome-wide linkage scans of attention deficit hyperactivity disorder." Am J Med Genet B Neuropsychiatr Genet, 147B(8): 1392-8.
Study Type	Genome-wide linkage study
Summary	Genetic contribution to the development of attention deficit hyperactivity disorder (ADHD) is well established. Seven independent genome-wide linkage scans have been performed to map loci that increase the risk for ADHD. Although significant linkage signals were identified in some of the studies, there has been limited replications between the various independent datasets. The current study gathered the results from all seven of the ADHD linkage scans and performed a Genome Scan Meta Analysis (GSMA) to identify the genomic region with most consistent linkage evidence across the studies. Genome-wide significant linkage (PSR=0.00034, POR=0.04) was identified on chromosome 16 between 64 and 83 Mb. In addition there are nine other genomic regions from the GSMA showing nominal or suggestive evidence of linkage. All these linkage results may be informative and focus the search for novel ADHD susceptibility genes.

Detail Info

Samples	Here, they apply the GSMA method to all seven published ADHD genome-wide linkage scans (Ogdie et al. [2003] Bakker et al. [2003] Arcos-Burgos et al. [2004] Hebebrand et al. [2006] Faraone et al. [2007] Asherson et al. [2008] Romanos et al. [2008]). The total number of cases is 2,084 of which 88% are Caucasian. All the studies applied the DSM-IV diagnostic criteria in the sample ascertainment process but used different data capture instruments. In some studies, cases with subthreshold diagnosis or comorbid autism were also included in the analysis. For the current meta-analysis, only linkage statistics based on the stringent diagnostic criteria were included. The four studies published earlier were genotyped on microsatellite panels mapped on the Marshfield genetic map while the three recent scans were genotyped with SNP microarrays mapped to the Decode genetic map [Kong et al., 2002].
Statistic Method	In the current study they used the GSMA program to get the summed rank SR, P_SR, and P_OR statistics through 10,000 permutations [Pardi et al., 2005]. The 22 autosomes were divided into 120 bins according to the original GSMA protocol and the genome-wide significant threshold is 0.05/120=0.000417, and the threshold for suggestive evidence of linkage is 0.0083 [Wise et al., 1999; Levinson et al., 2003]. The program HEGESMA was used to get the Q_ajusted and its P-values through 10,000 simulations [Zintzaras and Ioannidis, 2005b]. Both weighted and un-weighted GSMA analysis was performed.
Basic Result	Genome-wide significant linkage (PSR=0.00034, POR=0.04) was identified on chromosome 16 between 64 and 83 Mb. In addition there are nine other genomic regions from the GSMA showing nominal or suggestive evidence of linkage. All these linkage results may be informative and focus the search for novel ADHD susceptibility genes.

Regions reported by this study: 10

Region	Statistical Values	Author Comments	Result of Statistical Analysis
6p21.1-q15	SR=583, P_SR=0.04136, P_OR=0.208, P_het=0.77 from the un-weighted GSMA; SR=568, P_SR=0.06669, P_OR=0.255, P_het=0.83 from the weighted GSMA	nominal significant linkage nominal significant linkage	Trend
5p15.32-q14.3	SR=582, P_SR=0.04238, P_OR=0.111, P_het=0.76 from the un-weighted GSMA; SR=562, P_SR=0.07509, P_OR=0.151, P_het=0.86 from the weighted GSMA	nominal significant linkage nominal significant linkage	Trend
7p14.1-q21.11	SR=631, P_SR=0.01063, P_OR=0.368, Phet=0.45 from the un-weighted GSMA; SR=621, P_SR=0.01805, P_OR=0.371, P_het=0.27 from the weighted GSMA	nominal significant linkage nominal significant linkage	Trend
6q15-23.2	SR=577, P_{SR=0.04723, P_OR=0.036, P_het=0.76 from the un-weighted GSMA; SR=573, P_SR=0.06012, P_OR=0.436, P_het=0.64 from the weighted GSMA}	nominal significant linkage nominal significant linkage	Trend
9q21.32-31.1	SR=594, P_SR=0.03094, P_OR=0.15, P_het=0.4 from the un-weighted GSMA; SR=620, P_SR=0.01857, P_OR=0.174, P_het=0.4 from the weighted GSMA	nominal significant linkage nominal significant linkage	Trend
8p23.3	SR=595, P_SR=0.03054, P_OR=0.297, Phet=0.8 from the un-weighted GSMA; SR=567, P_SR=0.06843, P_OR=0.162, P_het=0.85 from the weighted GSMA	nominal significant linkage nominal significant linkage	Trend
16p13.3	SR=617, P_SR=0.01663, POR=0.322, P_het=0.47 from the un-weighted GSMA; SR=651, P_SR=0.00719, POR=0.211, P_het=0.55 from the weighted GSMA	nominal significant linkage nominal significant linkage	Significant
15p13	SR=578, P_SR=0.04611, P_OR=0.077, P_het=0.32 from the un-weighted GSMA; SR=571, P_SR=0.06325, P_OR=0.335, P_het=0.31 from the weighted GSMA	nominal significant linkage nominal significant linkage	Trend
17p13.3	SR=602, P_SR=0.02534, P_OR=0.361, P_het=0.69 from the un-weighted GSMA; SR=589, P_SR=0.04232, P_OR=0.226, P_het=0.55 from the weighted GSMA	nominal significant linkage nominal significant linkage	Trend
16q23.1-24.3	SR=714, P_SR=0.00034, P_OR=0.041, P_het=0.6 from the un-weighted GSMA; SR=718, P_SR=0.00038, POR=0.045, P_het=0.4 from the weighted GSMA	genome-wide significant linkage genome-wide significant linkage	Significant