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PMID: 15497111 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Attention-deficit/hyperactivity disorder in a population isolate: linkage to loci at 4q13.2, 5q33.3, 11q22, and 17p11.

American journal of human genetics ·Vol. 75 ·No. 6 ·2004-12-00 ·Pages 998-1014

Arcos-Burgos M, Castellanos FX, Pineda D, Lopera F, Palacio JD, Palacio LG, Rapoport JL, Berg K, Bailey-Wilson JE, Muenke M

Abstract

Attention-deficit/hyperactivity disorder (ADHD [MIM 143465]) is the most common behavioral disorder of childhood. Twin, adoption, segregation, association, and linkage studies have confirmed that genetics plays a major role in conferring susceptibility to ADHD. We applied model-based and model-free linkage analyses, as well as the pedigree disequilibrium test, to the results of a genomewide scan of extended and multigenerational families with ADHD from a genetic isolate. In these families, ADHD is highly comorbid with conduct and oppositional defiant disorders, as well as with alcohol and tobacco dependence. We found evidence of linkage to markers at chromosomes 4q13.2, 5q33.3, 8q11.23, 11q22, and 17p11 in individual families. Fine mapping applied to these regions resulted in significant linkage in the combined families at chromosomes 4q13.2 (two-point allele-sharing LOD score from LODPAL = 4.44 at D4S3248), 5q33.3 (two-point allele-sharing LOD score from LODPAL = 8.22 at D5S490), 11q22 (two-point allele-sharing LOD score from LODPAL = 5.77 at D11S1998; multipoint nonparametric linkage [NPL]-log[P value] = 5.49 at approximately 128 cM), and 17p11 (multipoint NPL-log [P value] >12 at approximately 12 cM; multipoint maximum location score 2.48 [alpha = 0.10] at approximately 12 cM; two-point allele-sharing LOD score from LODPAL = 3.73 at D17S1159). Additionally, suggestive linkage was found at chromosome 8q11.23 (combined two-point NPL-log [P value] >3.0 at D8S2332). Several of these regions are novel (4q13.2, 5q33.3, and 8q11.23), whereas others replicate already-published loci (11q22 and 17p11). The concordance between results from different analytical methods of linkage and the replication of data between two independent studies suggest that these loci truly harbor ADHD susceptibility genes.

MeSH Terms
Attention Deficit Disorder with Hyperactivity/genetics Chromosome Mapping Chromosomes, Human, Pair 11/genetics Chromosomes, Human, Pair 17/genetics Chromosomes, Human, Pair 4/genetics Chromosomes, Human, Pair 5/genetics Colombia Genetic Linkage/genetics Genome, Human Haplotypes/genetics Humans Lod Score Pedigree
Authors & Affiliations
10 authors, click to expand affiliations / ORCID
Arcos-Burgos Mauricio
National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3717, USA.
Castellanos F Xavier
Pineda David
Lopera Francisco
Palacio Juan David
Palacio Luis Guillermo
Rapoport Judith L
Berg Kate
Bailey-Wilson Joan E
Muenke Maximilian
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Article Info
Journal
American journal of human genetics
Abbr.
Am J Hum Genet
ISSN
0002-9297
DOI
10.1086/426154
Published
2004-12-00
Epub
2004-00-20
Pages
998-1014
Language
English
Region
United States
NLM ID
0370475
PMCID
PMC1182160
Subset
IM
External Links
PubMed source DOI: 10.1086/426154 PMC Full Text View journal details
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