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  Association and linkage of allelic variants of the dopamine transporter gene in ADHD

Friedel, S., Saar, K., Sauer, S., Dempfle, A., Walitza, S., Renner, T., et al. (2007). Association and linkage of allelic variants of the dopamine transporter gene in ADHD. Molecular Psychiatry, 12(10), 923-933. doi:10.1038/sj.mp.4001986.

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Genre: Journal Article
Alternative Title : Mol Psychiatry

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Friedel, S., Author
Saar, K., Author
Sauer, S.1, Author              
Dempfle, A., Author
Walitza, S., Author
Renner, T., Author
Romanos, M., Author
Freitag, C., Author
Seitz, C., Author
Palmason, H., Author
Scherag, A., Author
Windemuth-Kieselbach, C., Author
Schimmelmann, B. G., Author
Wewetzer, C., Author
Meyer, J., Author
Warnke, A., Author
Lesch, K. P., Author
Reinhardt, R.2, Author              
Herpertz-Dahlmann, B., Author
Linder, M., Author
Hinney, A., AuthorRemschmidt, H., AuthorSchäfer, H., AuthorKonrad, K., AuthorHübner, N., AuthorHebebrand, J., Author more..
Affiliations:
1Nutrigenomics and Gene Regulation (Sascha Sauer), Independent Junior Research Groups (OWL), Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1479662              
2High Throughput Technologies, Max Planck Institute for Molecular Genetics, Max Planck Society, ou_1433552              

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Free keywords: Attention-deficit/hyperactivity disorder; Haplotype; DAT1; SLC6A3
 Abstract: 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.

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Language(s): eng - English
 Dates: 2007-10
 Publication Status: Published in print
 Pages: -
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Title: Molecular Psychiatry
  Alternative Title : Mol Psychiatry
Source Genre: Journal
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Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 12 (10) Sequence Number: - Start / End Page: 923 - 933 Identifier: ISSN: 1359-4184