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.