Attention deficit hyperactivity disorder: fine mapping supports linkage to 5p13, 6q12, 16p13, and 17p11
Open accessAbstract
We completed fine mapping of nine positional candidate regions for attention-deficit/hyperactivity disorder (ADHD) in an extended population sample of 308 affected sibling pairs (ASPs), constituting the largest linkage sample of families with ADHD published to date. The candidate chromosomal regions were selected from all three published genomewide scans for ADHD, and fine mapping was done to comprehensively validate these positional candidate regions in our sample. Multipoint maximum LOD score (MLS) analysis yielded significant evidence of linkage on 6q12 (MLS 3.30; empiric P=.024) and 17p11 (MLS 3.63; empiric P=.015), as well as suggestive evidence on 5p13 (MLS 2.55; empiric P=.091). In conjunction with the previously reported significant linkage on the basis of fine mapping 16p13 in the same sample as this report, the analyses presented here indicate that four chromosomal regions--5p13, 6q12, 16p13, and 17p11--are likely to harbor susceptibility genes for ADHD. The refinement of linkage within each of these regions lays the foundation for subsequent investigations using association methods to detect risk genes of moderate effect size.
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Molecular genetic association studies, linkage studies, meta-analyses, and reviews have identified a number of genes that might contribute to the onset of childhood ADHD, including dopamine receptor genes, dopamine-beta-hydroxylase, dopamine transporter gene, norepinephrine transporter gene, noradrenergic receptor genes, MAO-A, COMT, serotonin receptor and transporter genes, and GABRB3.
“have identified a number of genes that might contribute to the onset of childhood ADHD (cADHD), including, but not limited to, dopamine receptor genes such as DRD4, DRD5, DRD2, DRD3, dopamine-beta-hydroxylase (DBH), dopamine transporter gene (DAT, SLC6A3)”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Ogdie et al., 2004
The etiology section (page unavailable) reports replicated, though inconsistent and small, associations for DAT1, DRD4, and DRD5; the References also identify ADHD studies of DBH and serotonin-related genes. Our copy does not substantiate the full attributed list, including DRD2, DRD3, MAO-A, COMT, and GABRB3. (LLM, conf=0.88)
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- Authors
- Ogdie, M. N., Fisher, S. E., Yang, M., Ishii, J., Francks, C., Loo, S. K., Cantor, R. M., McCracken, J. T., McGough, J. J., Smalley, S. L., & Nelson, S. F.
- Affiliations
- University of California, Los Angeles (US)
- Centre for Human Genetics (GB)
- Corresponding author
- Nelson, Stanley F.
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2004-10
- Volume
- 75
- Issue
- 4
- Pages
- 661-668
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC1182053
- OpenAlex
- W2130684484
- Cited by
- 133
- References
- 51
- Citations by year
- 2026: 1 · 2025: 1 · 2024: 3 · 2022: 1 · 2020: 2 · 2019: 2 · 2018: 2 · 2017: 3 · 2016: 3 · 2015: 8 · 2014: 6 · 2013: 1 · 2012: 6
- FWCI
- 8.29
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- The American Journal of Human Genetics (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- eScholarship (California Digital Library) (submittedVersion)
- MPG.PuRe (Max Planck Society) (submittedVersion, other-oa)
- Funders
- National Institute of Mental Health (MH 58277, R01MH058277, MH 01805, MH01969, K24MH001805)
- National Institute of General Medical Sciences (T32GM007104, GM 07104)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetics and Neurodevelopmental Disorders
- Keywords
- attention deficit hyperactivity disorder, genetic linkage, fine mapping, affected sibling pairs, susceptibility genes
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Chromosome Mapping, Chromosomes, Human, Pair 16, Chromosomes, Human, Pair 17, Chromosomes, Human, Pair 5, Chromosomes, Human, Pair 6, Genetic Markers, Humans, Lod Score, Siblings
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