ADHDgene Database

Hot Results

Quick Search

Keyword:
Type:

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	Friedel S, 200717579611
Citation	Friedel S., Saar K., Sauer S., Dempfle A., Walitza S., Renner T., Romanos M., Freitag C., Seitz C., Palmason H., Scherag A., Windemuth-Kieselbach C., Schimmelmann B. G., Wewetzer C., Meyer J., Warnke A., Lesch K. P., Reinhardt R., Herpertz-Dahlmann B., Linder M., Hinney A., Remschmidt H., Schafer H., Konrad K., Hubner N. and Hebebrand J. (2007) "Association and linkage of allelic variants of the dopamine transporter gene in ADHD." Mol Psychiatry, 12(10): 923-33.
Study Design	family-based
Study Type	Candidate-gene association study
Sample Size	523 cases from 329 families
Predominant Ethnicity	Caucasian
Population	Germany
Gender	404 males (77.25%) and 119 females
Age Group	Children/Adolescents : mean age 11.1 years (SD=3.0)

Detail Info

Summary	Previously, they had reported a genome-wide scan for ADHD in 102 families with affected sibs of German ancestry; the highest multipoint LOD score of 4.75 was obtained on chromosome 5p13 near the dopamine transporter gene (DAT1). They genotyped 30 SNPs in this candidate gene and its 50 region in 329 families (including the 102 initial families) with 523 affected offspring. They have accumulated evidence that genetic variation at the DAT1 locus underlies their ADHD linkage peak on chromosome 5; additionally solid association for a single SNP and a haplotype were shown. Future studies are required to assess if variation at this locus also explains other positive linkage results obtained for chromosome 5p.
Total Sample	In total, 523 ADHD children from 329 families were included. In 173, 123, 28 and 5 families, one, two, three and four affected children were recruited, respectively.
Sample Collection	Samples were collected from six child psychiatric outpatient units (Aachen, Marburg, Homburg, Trier, Regensburg and Wuerzburg) in Germany. All families were of Caucasian descent; the vast majority of families were of German origin.
Diagnosis Description	Families were included if at least one child was diagnosed with ADHD according to DSM- IV. The ascertainment strategy and inclusion criteria have been described previously (Hebebrand J. et al., 2006). DSM-IV diagnosis of ADHD in children from Homburg and Trier (n=72) was derived from a semi-structured standardized interview with parents (Kinder-DIPS) and the Conners' Parent and Teacher Rating Scales.
Technique	Genotyping of 7 SNPs was performed using the GOOD assay and matrix assisted laser disorption/ionisation (MALDI) mass spectrometry negative ion mode detection. PCR, primer extension, phosphodiesterase II digestion, alkylation and sample preparation were performed as described using MTP AnchorChip 400/384 targets from BrUnited Kingdomer Daltonics (Bremen, Germany). Data analysis was performed as described recently using the GenoTools SNP Manager software (BrUnited Kingdomer Daltonics). The other 5 SNPs were genotyped using TaqMan assays (Applied Biosystems, Foster City, CA, USA) using FAM and VIC reporter dyes. All TaqMan probes and primers were purchased from Applied Biosystems. They used the ABI Prism 7900HT Sequence detection instrument (Applied Biosystems, Darmstadt, Germany) for thermocycling and data collection. Frag- ments DAT1 8, 10 and 11 (according to 25) were resequenced.DNA sequences were determined using ABI BigDye Terminator 3.1 chemistry and 3730xl ABI 96-capillary sequencer systems. Sequences were processed for quality clipping and assembled using an in-house software package based on the poly-phred system.
Analysis Method	Marker data were checked for Mendelian inconsistencies using PedCheck. Hardy-Weinberg equilibrium was checked on parental genotypes by chi-square tests as implemented in Pedstats. Likely genotyping errors were checked using FAMHAP. Haploview was used to calculate linkage disequilibrium. A family-based association test (TDT) was performed for the 23 SNPs with a MAF>3% in the DAT1 by using a permutation test as implemented in FAMHAP. Allele frequencies for linkage analysis were estimated from all parental alleles. Multipoint nonparametric linkage analysis was performed on the qualitative affection status ADHD using the Sall statistic that can be converted to a nonparametric LOD score as implemented in Merlin. Post hoc analyses were performed both for the original 102 GS families and the 156 families with affected sib pairs (ASPs). The genotype-IBD sharing test (GIST) was used to test whether probands with a certain genotype (under a dominant model) contributed more than expected to the linkage signal. LAMP software was used to test whether one of the SNPs is in complete or partial LD with a putative disease locus in this region, for example, whether it can explain the observed linkage.
Result Description	They found that (1) SNP rs463379 was significantly associated with ADHD upon correction for multiple testing (P-value=0.0046); (2) the global P-value for association of haplotypes was significant for block two upon correction for all (n=3) tested blocks (P-value=0.0048); (3) within block two they detected a nominal P-value=0.000034 for one specific marker combination. This CGC haplotype showed relative risks of 1.95 and 2.43 for heterozygous and homozygous carriers, respectively; and (4) finally, their linkage data and the genotype-IBD sharing test (GIST) suggest that genetic variation at the DAT1 locus explains their linkage peak and that rs463379 (P-value<0.05) is the only SNP of the above haplotype that contributed to the linkage signal.

SNPs reported by this study (count: 22)

SNP	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
rs8179029	G/A	G	FAMHAP P-value=0.14 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs7732456	A/C	A	FAMHAP P-value=0.77 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs37022	T/A	T	FAMHAP P-value=0.15 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs28362317	A/T	A	FAMHAP P-value=0.13 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs403636	G/T	G	FAMHAP P-value=0.01 in single marker association analysis	not significantly associated with ADHD after multiple test c...... not significantly associated with ADHD after multiple test correction More...	Significant
rs3756450	T/C	T	FAMHAP P-value=0.03 in single marker association analysis	not significantly associated with ADHD after multiple test c...... not significantly associated with ADHD after multiple test correction More...	Significant
rs464049	T/C	T	FAMHAP P-value=0.13 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs463379	C/G	C	FAMHAP P-value=0.0002 in single marker association analysis	significantly associated with ADHD upon correction for multi...... significantly associated with ADHD upon correction for multiple testing (P-value=0.0046) More...	Significant
rs6350	C/T	C	FAMHAP P-value=0.008 in single marker association analysis	not significantly associated with ADHD after multiple test c...... not significantly associated with ADHD after multiple test correction More...	Significant
rs6347	A/G	A	FAMHAP P-value=1 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs1316830	G/A	G	FAMHAP P-value=0.03 in single marker association analysis	not significantly associated with ADHD after multiple test c...... not significantly associated with ADHD after multiple test correction More...	Significant
rs2042449	C/T	C	FAMHAP P-value=0.78 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs2550956	C/T	T	FAMHAP P-value=0.66 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs2617595	A/G	A	FAMHAP P-value=0.29 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs2652509	C/T	C	FAMHAP P-value=0.35 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs2652510	G/A	A	FAMHAP P-value=0.43 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs27048	C/T	G	FAMHAP P-value=0.24 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs27072	C/T	C	FAMHAP P-value=0.85 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs11133767	G/A	A	FAMHAP P-value=0.74 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs11564750	C/G	C	FAMHAP P-value=0.19 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs11564752	G/T	G	FAMHAP P-value=0.56 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant
rs11564774	C/G	G	FAMHAP P-value=0.59 in single marker association analysis	No association was found with ADHD No association was found with ADHD	Non-significant

Other variant reported by this study (count: 1)

Variant Name	Allele Change	Risk Allele	Statistical Values	Author Comments	Result of Statistical Analysis
SLC6A3 intron1 sid1153	ins(C)	WT	FAMHAP P-value=0.1 in single marker association analysis FAMHAP P-value=0.1 in single marker association analysis	No association was found with ADHD	Non-significant

Genes reported by this study (count: 1)