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          Institute: MPI für molekulare Genetik     Collection: Department of Vertebrate Genomics     Display Documents

ID: 334133.0, MPI für molekulare Genetik / Department of Vertebrate Genomics
Association and linkage of allelic variants of the dopamine transporter gene in ADHD
Authors: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.; Schäfer, H.; Konrad, K.; Hübner, N.; Hebebrand, J.
Date of Publication (YYYY-MM-DD):2007-10
Title of Journal:Molecular Psychiatry
Journal Abbrev.:Mol Psychiatry
Issue / Number:10
Start Page:923
End Page:933
Copyright:© 2008 Nature Publishing Group
Review Status:not specified
Audience:Experts Only
Abstract / Description:Previously, we had reported a genome-wide scan for attention-deficit/hyperactivity disorder (ADHD) in 102 families with affected sibs of German ancestry; the highest multipoint LOD score of 4.75 was obtained on chromosome 5p13 (parametric HLOD analysis under a dominant model) near the dopamine transporter gene (DAT1). We genotyped 30 single nucleotide polymorphisms (SNPs) in this candidate gene and its 5' region in 329 families (including the 102 initial families) with 523 affected offspring. We found that (1) SNP rs463379 was significantly associated with ADHD upon correction for multiple testing (P=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=0.0048); (3) within block two we detected a nominal P=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, our linkage data and the genotype-IBD sharing test (GIST) suggest that genetic variation at the DAT1 locus explains our linkage peak and that rs463379 (P<0.05) is the only SNP of the above haplotype that contributed to the linkage signal. In sum, we have accumulated evidence that genetic variation at the DAT1 locus underlies our 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.
Free Keywords:Attention-deficit/hyperactivity disorder; Haplotype; DAT1; SLC6A3
External Publication Status:published
Document Type:Article
Communicated by:Hans Lehrach
Affiliations:MPI für molekulare Genetik
External Affiliations:Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany;
Max Delbrück Center for Molecular Medicine (MDC), Berlin-Buch, Germany;
Institute of Medical Biometry and Epidemiology, Philipps-University, Marburg, Germany;
Department of Child and Adolescent Psychiatry and Psychotherapy, Julius-Maximilians-University, Würzburg, Germany;
Department of Child and Adolescent Psychiatry, Saarland University Hospital, Homburg (Saar), Germany;
Department of Neuro-Behavioral Genetics, University of Trier, Trier, Germany;
Molecular and Clinical Psychobiology, Department of Psychiatry and Psychotherapy, Julius-Maximilians-University, Würzburg, Germany;
Department of Child and Adolescent Psychiatry and Psychotherapy, RWTH Aachen University, Aachen, Germany;
Department of Child and Adolescent Psychiatry, Regensburg, Germany;
Department of Child and Adolescent Psychiatry, Philipps-University, Marburg, Germany
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