A genome-wide scan for attention-deficit/hyperactivity disorder in 155 German sib-pairs.
Three groups have previously performed genome scans in attention-deficit/hyperactivity disorder (ADHD); linkage to chromosome 5p13 was detected in all of the respective studies. In the current study, we performed a whole-genome scan with 102 German families with two or more offspring who currently fulfilled the diagnostic criteria for ADHD. Including subsequent fine mapping on chromosome 5p, a total of 523 markers were genotyped. The highest nonparametric multipoint LOD score of 2.59 (empirical genome-wide significance 0.1) was obtained for chromosome 5p at 17 cM (according to the Marshfield map). Subsequent analyses revealed (a) a higher LOD score of 3.37 at 39 cM for a quantitative severity score based on symptoms of inattention than for hyperactivity/impulsivity (LOD score of 1.11 at 59 cM), and (b) an HLOD of 4.75 (empirical genome-wide significance 0.001) based on a parametric model assuming dominant inheritance. The locus of the solute carrier 6A3 (SLC6A3; dopamine transporter 1; DAT1) localizes to 5p15.33; the gene has repeatedly been implicated in the etiology of ADHD. However, in our sample the DAT1 VNTR did not show association with ADHD. We additionally identified nominal evidence for linkage to chromosomes 6q, 7p, 9q, 11 q, 12q and 17p, which had also been identified in previous scans. Despite differences in ethnicity, ascertainment and phenotyping schemes, linkage results in ADHD appear remarkably consistent.
Hebebrand
J
J
Department of Child and Adolescent Psychiatry, University of Duisburg-Essen, Essen, Germany. Johannes.Hebebrand@uni-duisburg-essen.de
Dempfle
A
A
Saar
K
K
Thiele
H
H
Herpertz-Dahlmann
B
B
Linder
M
M
Kiefl
H
H
Remschmidt
H
H
Hemminger
U
U
Warnke
A
A
Knölker
U
U
Heiser
P
P
Friedel
S
S
Hinney
A
A
Schäfer
H
H
Nürnberg
P
P
Konrad
K
K
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000145:classification / Q000235:genetics*; D002648:Child; D002874:Chromosome Mapping; D002877:Chromosomes, Human / Q000235:genetics*; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D015894:Genome, Human; D005858:Germany; D006801:Humans; D008126:Lod Score; D008297:Male; D018895:Microsatellite Repeats; D010375:Pedigree; D035781:Siblings; D018709:Statistics, Nonparametric
D050483:Dopamine Plasma Membrane Transport Proteins; C493214:SLC6A3 protein, human