Partial replication of a DRD4 association in ADHD individuals using a statistically derived quantitative trait for ADHD in a family-based association test
Abstract
Background Previous research found an association between single nucleotide polymorphisms (SNPs) in the promoter region of DRD4 and statistically derived phenotypes generated from attention-deficit/hyperactivity disorder (ADHD) symptoms. We sought to replicate this finding by using the same methodology in an independent sample of ADHD individuals.Methods Four SNPs were genotyped in and around DRD4 in 2631 individuals in 642 families. We developed a quantitative phenotype at each SNP by weighting nine inattentive and nine hyperactive-impulsive symptoms. The weights were selected to maximize the heritability at each SNP. Once a quantitative phenotype was generated at each SNP, the screening procedure implemented in PBAT was used to select and test the five SNPs/genetic model combinations with the greatest power to detect an association for DRD4.Results One of the four SNPs was associated with the quantitative phenotypes generated from the ADHD symptoms (corrected p-values = .02). A rank ordering of the correlation between each of the ADHD symptoms and the quantitative phenotype suggested that hyperactive-impulsive symptoms were more strongly correlated with the phenotype; however, including inattentive symptoms was necessary to achieve a significant result.Conclusions This study partially replicated a previous finding by identifying an association between rs7124601 and a quantitative trait generated from ADHD symptoms. The rs7124601 is in linkage disequilibrium (LD) with the SNPs identified previously. In contrast to the previous study, this finding suggests that both hyperactive-impulsive and inattentive symptoms are important in the association.
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Evidence on whether DRD4 is more strongly associated with inattentive symptoms than hyperactive-impulsive symptoms of ADHD is inconsistent, with some studies finding a stronger inattentive association and others finding association with both symptom domains.
“Several studies have suggested that DRD4 is more strongly associated with inattentive symptoms than hyperactive-impulsive symptoms of ADHD (McCracken et al., 2000; Gizer and Waldman, 2012), while other studies showed that DRD4 was implicated in both inattentive and hyperactive symptoms (Lasky-Su et al., 2007; Bidwell et al., 2011).”
From A Review of Heterogeneity in Attention Deficit/Hyperactivity Disorder (ADHD) (2019) · cites this paper as Lasky-Su et al., 2007
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- Authors
- Lasky-Su, J., Banaschewski, T., Buitelaar, J., Franke, B., Brookes, K., Sonuga-Barke, E., Ebstein, R., Eisenberg, J., Gill, M., Manor, I., Miranda, A., Mulas, F., Oades, R. D., Roeyers, H., Rothenberger, A., Sergeant, J., Steinhausen, H.-C., Taylor, E., Zhou, K., Thompson, M., Asherson, P., & Faraone, S. V.
- Affiliations
- SUNY Upstate Medical University (US)
- University of Göttingen (DE)
- Radboud University Nijmegen (NL)
- University of Southampton (GB)
- Herzog Hospital (IL)
- Geha Mental Health Center (IL)
- St. James's Hospital (IE)
- Universitat de València (ES)
- Ghent University (BE)
- Vrije Universiteit Amsterdam (NL)
- University of Zurich (CH)
- Corresponding author
- Faraone, Stephen V.
- ORCID
- Venue
- Biological Psychiatry
- Publisher
- Elsevier BV
- Published
- 2007-11
- Volume
- 62
- Issue
- 9
- Pages
- 985-990
- ISSN
- 0006-3223 (ISSN-L)
- OpenAlex
- W2150934124
- Cited by
- 29
- References
- 27
- Citations by year
- 2024: 1 · 2020: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 2 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 3.22
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biological Psychiatry (publishedVersion)
- PubMed (publishedVersion)
- Ghent University Academic Bibliography (Ghent University) (submittedVersion)
- DuEPublico (University of Duisburg-Essen) (submittedVersion)
- ePrints Soton (University of Southampton) (submittedVersion)
- Research Portal (King's College London) (submittedVersion)
- GRO (submittedVersion)
- Radboud Repository (Radboud University) (submittedVersion)
- Funders
- National Institute of Mental Health (R01 MH 62873, R01MH062873)
- 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 › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Keywords
- attention deficit hyperactivity disorder, DRD4, dopamine D4 receptor, promoter, single nucleotide polymorphisms, quantitative phenotypes, heritability, hyperactive-impulsive symptoms, inattentive symptoms, linkage disequilibrium, family-based association test, replication
- MeSH terms
- Adolescent, Attention Deficit Disorder with Hyperactivity, Child, Child, Preschool, Europe, Family Health, Female, Humans, Male, Phenotype, Promoter Regions, Genetic, Severity of Illness Index, Databases, Factual, Quantitative Trait, Heritable, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Receptors, Dopamine D4
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