Neuropsychological endophenotype approach to genome-wide linkage analysis identifies susceptibility loci for ADHD on 2q21.1 and 13q12.11
Open accessAbstract
ADHD linkage findings have not all been consistently replicated, suggesting that other approaches to linkage analysis in ADHD might be necessary, such as the use of (quantitative) endophenotypes (heritable traits associated with an increased risk for ADHD). Genome-wide linkage analyses were performed in the Dutch subsample of the International Multi-Center ADHD Genetics (IMAGE) study comprising 238 DSM-IV combined-type ADHD probands and their 112 affected and 195 nonaffected siblings. Eight candidate neuropsychological ADHD endophenotypes with heritabilities > 0.2 were used as quantitative traits. In addition, an overall component score of neuropsychological functioning was used. A total of 5407 autosomal single-nucleotide polymorphisms (SNPs) were used to run multipoint regression-based linkage analyses. Two significant genome-wide linkage signals were found, one for Motor Timing on chromosome 2q21.1 (LOD score: 3.944) and one for Digit Span on 13q12.11 (LOD score: 3.959). Ten suggestive linkage signals were found (LOD scores > or = 2) on chromosomes 2p, 2q, 3p, 4q, 8q, 12p, 12q, 14q, and 17q. The suggestive linkage signal for the component score that was found at 2q14.3 (LOD score: 2.878) overlapped with the region significantly linked to Motor Timing. Endophenotype approaches may increase power to detect susceptibility loci in ADHD and possibly in other complex disorders.
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Recent studies found new genetic regions associated with ADHD-related endophenotypes, including Latrophilin 3, Fibroblast growth factor 1, and Cholinergic receptor nicotinic alpha 4.
“Several recent studies found new genetic regions associated with ADHD-related endophenotypes, including Latrophilin 3 gene, Fibroblast growth factor 1 gene, Cholinergic receptor, nicotinic, alpha 4, et cetera (Rommelse et al., 2008; Mastronardi et al., 2016).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Rommelse et al., 2008
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ADHD Endophenotypes in Caribbean Families
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Coordinatewise Gaussianization: Theories and Applications
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Cognitive Control in Attention Deficit Hyperactivity Disorder
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When Is EEG Indicated in Attention-Deficit/Hyperactivity Disorder?
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- Authors
- Rommelse, N. N. J., Arias-Vásquez, A., Altink, M. E., Buschgens, C. J. M., Fliers, E., Asherson, P., Faraone, S. V., Buitelaar, J. K., Sergeant, J. A., Oosterlaan, J., & Franke, B.
- Affiliations
- Radboud University Nijmegen (NL)
- King's College London (GB)
- SUNY Upstate Medical University (US)
- Vrije Universiteit Amsterdam (NL)
- Corresponding author
- Franke, Barbara
- ORCID
- Venue
- The American Journal of Human Genetics
- Publisher
- Elsevier BV
- Published
- 2008-07
- Volume
- 83
- Issue
- 1
- Pages
- 99-105
- ISSN
- 0002-9297 (ISSN-L)
- PMC
- PMC2443830
- OpenAlex
- W2027464692
- Cited by
- 75
- References
- 35
- Citations by year
- 2026: 1 · 2025: 2 · 2022: 1 · 2021: 1 · 2020: 1 · 2019: 3 · 2018: 1 · 2017: 2 · 2016: 3 · 2015: 10 · 2014: 6 · 2013: 3 · 2012: 6
- FWCI
- 8.20
- 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)
- VU Research Portal (publishedVersion, other-oa)
- Digital Academic REpository of VU University Amsterdam (Vrije Universiteit Amsterdam) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion, other-oa)
- Funders
- Eli Lilly and Company
- National Institute of Mental Health (R01MH062873, R01 MH62873-01A1)
- Cilag
- 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 › Genetic Mapping and Diversity in Plants and Animals
- Keywords
- attention deficit hyperactivity disorder, ADHD genetics, genome-wide linkage analysis, genetic susceptibility loci, motor timing, digit span, heritability, image studies
- MeSH terms
- Attention Deficit Disorder with Hyperactivity, Child, Chromosome Mapping, Chromosomes, Human, Pair 13, Chromosomes, Human, Pair 2, Cognition, Female, Humans, Genetic Linkage, Lod Score, Male, Motor Activity, Netherlands, Neuropsychology, Phenotype, Regression Analysis, Case-Control Studies, Genome, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Siblings, Quantitative Trait Loci
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