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Mol Psychiatry. 2008 May;13(5):522-30. doi: 10.1038/mp.2008.12. Epub 2008 Feb 26.

Genome-wide linkage analysis of ADHD using high-density SNP arrays: novel loci at 5q13.1 and 14q12.

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  • 1ADHD Clinical Research Program, Department of Child and Adolescent Psychiatry and Psychotherapy, University of Wuerzburg, Wuerzburg, Germany. Romanos@kjp.uni-wuerzburg.de

Abstract

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.

PMID:
18301393
[PubMed - indexed for MEDLINE]
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