Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13.1 and 14q12.
Previous genome-wide linkage studies applied the affected sib-pair design; one investigated extended pedigrees of a genetic isolate. Here, results of a genome-wide high-density linkage scan of attention-deficit/hyperactivity disorder (ADHD) using an array-based genotyping of approximately 50 K single nucleotide polymorphism (SNPs) markers are presented. We investigated eight extended pedigrees of German origin that were non-related, not part of a genetic isolate and ascertained on the basis of clinical referral. Two parametric analyses maximizing LOD scores (MOD) and a non-parametric analysis for both a broad and a narrow phenotype approach were conducted. Novel linkage loci across all families were detected at 2q35, 5q13.1, 6q22-23 and 14q12, within individual families at 18q11.2-12.3. Further linkage regions at 7q21.11, 9q22 and 16q24.1 in all families, and at 1q25.1, 1q25.3, 9q31.1-33.1, 9q33, 12p13.33, 15q11.2-13.3 and 16p12.3-12.2 in individual families replicate previous findings. High-resolution linkage mapping points to several novel candidate genes characterized by dense expression in the brain and potential impact on disorder-relevant synaptic transmission. Our study provides further evidence for common gene effects throughout different populations despite the complex multifactorial etiology of ADHD.
Romanos
M
M
ADHD Clinical Research Program, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany. Romanos@kjp.uni-wuerzburg.de
Freitag
C
C
Jacob
C
C
Craig
D W
DW
Dempfle
A
A
Nguyen
T T
TT
Halperin
R
R
Walitza
S
S
Renner
T J
TJ
Seitz
C
C
Romanos
J
J
Palmason
H
H
Reif
A
A
Heine
M
M
Windemuth-Kieselbach
C
C
Vogler
C
C
Sigmund
J
J
Warnke
A
A
Schäfer
H
H
Meyer
J
J
Stephan
D A
DA
Lesch
K P
KP
D000293:Adolescent; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology / Q000235:genetics*; D002648:Child; D002883:Chromosomes, Human, Pair 14 / Q000235:genetics*; D002895:Chromosomes, Human, Pair 5 / Q000235:genetics*; D005260:Female; D005838:Genotype; D005858:Germany / Q000453:epidemiology; D006801:Humans; D008126:Lod Score; D008297:Male; D015588:Observer Variation; D020411:Oligonucleotide Array Sequence Analysis; D010375:Pedigree; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D018709:Statistics, Nonparametric