Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study
Open accessAbstract
Attention-deficit/hyperactivity disorder (ADHD) is a common and highly heritable developmental disorder characterized by a persistent impairing pattern of inattention and/or hyperactivity-impulsivity. Using families from a genetic isolate, the Paisa population from Colombia, and five independent datasets from four different populations (United States, Germany, Norway and Spain), a highly consistent association was recently reported between ADHD and the latrophilin 3 (LPHN3) gene, a brain-specific member of the LPHN subfamily of G-protein-coupled receptors that is expressed in ADHD-related regions, such as amygdala, caudate nucleus, cerebellum and cerebral cortex. To replicate the association between LPHN3 and ADHD in adults, we undertook a case-control association study in 334 adult patients with ADHD and 334 controls with 43 single nucleotide polymorphisms (SNPs) covering the LPNH3 gene. Single- and multiple-marker analyses showed additional evidence of association between LPHN3 and combined type ADHD in adulthood [P = 0.0019; df = 1; odds ratio (OR) = 1.82 (1.25-2.70) and P = 5.1e-05; df = 1; OR = 2.25 (1.52-3.34), respectively]. These results further support the LPHN3 contribution to combined type ADHD, and specifically to the persistent form of the disorder, and point at this new neuronal pathway as a common susceptibility factor for ADHD throughout the lifespan.
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GWAS have indicated genes playing a role in ADHD that could be linked to neuronal plasticity mechanisms or to deficiencies in synthesis or release of neurotransmitters, mainly DA, but also serotonin and NE.
“Genome-wide association studies (GWAS) have indicated genes playing a role in ADHD that could be linked to neuronal plasticity mechanisms (neuronal migration, cell adhesion and neuron proliferation) [61] or to deficiencies in the synthesis or release of neurotransmitters (NTs), mainly DA, but also serotonin and NE [56, 62].”
From Molecular Characterisation of the Mechanism of Action of Stimulant Drugs Lisdexamfetamine and Methylphenidate on ADHD Neurobiology: A Review (2022) · cites this paper as [61]
The passage indexed under Abstract (page not supplied) says dopaminergic and serotonergic candidate genes have been examined in ADHD and suggests that the LPHN receptor family is involved in synaptic neurotransmitter release. It does not establish deficiencies in neurotransmitter synthesis or release, mention norepinephrine, or present these findings as GWAS results. The separate neuronal-plasticity clause is attached to citation [61], not this source. (LLM, conf=0.86)
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Cites
Molecular genetics of attention-deficit/hyperactivity disorder
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Research works printed but not linked: 2
- Arcos-Burgos, M., Jain, M., Acosta, M.T. et al. (in press) A common variant of the latrophilin 3 gene, LPHN3, confers susceptibility to Genes, Brain and Behavior (2011) 10: 149-157 ADHD and predicts effectiveness of stimulant medication. Mol Psychiatry (in press).
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Synaptic Neurexin Complexes: A Molecular Code for the Logic of Neural Circuits
Südhof, T. C. (2017) · Cell · doi:10.1016/j.cell.2017.10.024 · Cited by 810 · see citing works
The genetics of attention deficit/hyperactivity disorder in adults, a review
on behalf of the International Multicentre persistent ADHD CollaboraTion (IMpACT), Franke, B., Faraone, S. V., Asherson, P., Buitelaar, J., Bau, C. H. D., Ramos-Quiroga, J. A., Mick, E., Grevet, E. H., Johansson, S., et al. (2012) · Molecular Psychiatry · doi:10.1038/mp.2011.138 · Cited by 432 · see citing works
Self-citationBonvicini, C., Faraone, S. V., & Scassellati, C. (2018) · The World Journal of Biological Psychiatry · doi:10.1080/15622975.2017.1282175 · Cited by 83 · see citing works
Quintero, J., Gutiérrez-Casares, J. R., & Álamo, C. (2022) · Neurology and Therapy · doi:10.1007/s40120-022-00392-2 · Cited by 70 · see citing works
“plasticity mechanisms (neuronal migration, cell adhesion and neuron proliferation) [61] or to deficiencies in the synthesis or release of neurotransmitters (NTs), mainly DA, but also serotonin and NE [56, 62].”
BackgroundA common genetic network underlies substance use disorders and disruptive or externalizing disorders
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Self-citationQuantitative and Molecular Genetics of ADHD
Asherson, P., & Gurling, H. (2011) · Current Topics in Behavioral Neurosciences · doi:10.1007/7854_2011_155 · Cited by 43 · see citing works
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Sánchez‐Mora, C., Richarte, V., Garcia‐Martínez, I., Pagerols, M., Corrales, M., Bosch, R., Vidal, R., Viladevall, L., Casas, M., Cormand, B., et al. (2015) · American Journal of Medical Genetics Part B: Neuropsychiatric Genetics · doi:10.1002/ajmg.b.32340 · Cited by 23 · see citing works
Self-citation
- Authors
- Ribasés, M., Ramos-Quiroga, J. A., Sánchez-Mora, C., Bosch, R., Richarte, V., Palomar, G., Gastaminza, X., Bielsa, A., Arcos-Burgos, M., Muenke, M., Castellanos, F. X., Cormand, B., Bayés, M., & Casas, M.
- Affiliations
- Vall d'Hebron Hospital Universitari (ES)
- National Institutes of Health (US)
- Nathan Kline Institute for Psychiatric Research (US)
- Centro de Investigación Biomédica en Red (ES)
- Centro Nacional de Análisis Genómico (ES)
- Universitat Autònoma de Barcelona (ES)
- Corresponding author
- Ribasés, M.
- Venue
- Genes, Brain and Behavior
- Publisher
- Wiley
- Published
- 2010-11-04
- Volume
- 10
- Issue
- 2
- Pages
- 149-157
- ISSN
- 1601-183X (ISSN-L)
- 1601-1848
- OpenAlex
- W2096349664
- Cited by
- 119
- References
- 3
- Citations by year
- 2026: 4 · 2025: 4 · 2024: 3 · 2023: 5 · 2022: 12 · 2021: 12 · 2020: 5 · 2019: 12 · 2018: 7 · 2017: 9 · 2016: 7 · 2015: 6 · 2014: 6 · 2013: 5 · 2012: 14
- FWCI
- 5.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Genes Brain & Behavior (publishedVersion)
- PubMed (publishedVersion)
- ANU Open Research (Australian National University) (submittedVersion)
- Funders
- Generalitat de Catalunya
- National Institutes of Health
- Agència de Gestió d'Ajuts Universitaris i de Recerca (2009GR00971)
- Instituto de Salud Carlos III
- National Human Genome Research Institute
- NHLBI Division of Intramural Research
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Attention Deficit Hyperactivity Disorder
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neurotransmitter Receptor Influence on Behavior
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Genetics › Genetic Associations and Epidemiology
- Keywords
- attention deficit hyperactivity disorder, LPHN3, genetic susceptibility, adult ADHD, combined type ADHD, G protein-coupled receptors, single nucleotide polymorphisms, genetic association, replication study, persistent ADHD
- MeSH terms
- Adult, Attention Deficit Disorder with Hyperactivity, DNA, Female, Genetic Markers, Genotype, Haplotypes, Humans, Male, Neuropsychological Tests, Quality Control, Spain, Linkage Disequilibrium, Case-Control Studies, Receptors, Peptide, Genetic Predisposition to Disease, Polymorphism, Single Nucleotide, Diagnostic and Statistical Manual of Mental Disorders, Receptors, G-Protein-Coupled
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