The involvement of the canonical Wnt-signaling receptor LRP5 and LRP6 gene variants with ADHD and sexual dimorphism: Association study and meta-analysis.

Adolescent Adult Attention Deficit Disorder with Hyperactivity / genetics Child Female Genetic Variation / genetics Humans Low Density Lipoprotein Receptor-Related Protein-5 / genetics Low Density Lipoprotein Receptor-Related Protein-6 / genetics Male Sex Characteristics Sex Factors Wnt Signaling Pathway / genetics
SNP attention-deficit hyperactivity disorder gender genetics polymorphism

Journal

American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics
ISSN: 1552-485X
Titre abrégé: Am J Med Genet B Neuropsychiatr Genet
Pays: United States
ID NLM: 101235742

Informations de publication

Date de publication:
09 2019
Historique:
received: 06 03 2018
revised: 27 09 2018
accepted: 05 10 2018
pubmed: 27 11 2018
medline: 16 7 2020
entrez: 27 11 2018
Statut: ppublish

Résumé

Wnt-signaling is one of the most abundant pathways involved in processes such as cell-proliferation, -polarity, and -differentiation. Altered Wnt-signaling has been linked with several neurodevelopmental disorders including attention-deficit/hyperactivity disorder (ADHD) as well as with cognitive functions, learning and memory. Particularly, lipoprotein receptor-related protein 5 (LRP5) or LRP6 coreceptors, responsible in the activation of the canonical Wnt-pathway, were associated with cognitive alterations in psychiatric disorders. Following the hypothesis of Wnt involvement in ADHD, we investigated the association of genetic variations in LRP5 and LRP6 genes with three independent child and adolescent ADHD (cADHD) samples (total 2,917 participants), followed by a meta-analysis including previously published data. As ADHD is more prevalent in males, we stratified the analysis according to sex and compared the results with the recent ADHD Psychiatric Genomic Consortium (PGC) GWAS. Meta-analyzing our data including previously published cADHD studies, association of LRP5 intronic rs4988319 and rs3736228 (Ala1330Val) with cADHD was observed among girls (OR = 1.80 with 95% CI = 1.07-3.02, p = .0259; and OR = 2.08 with 95% CI = 1.01-4.46, p = .0026, respectively), whereas in boys association between LRP6 rs2302685 (Val1062Ile) and cADHD was present (OR = 1.66, CI = 1.20-2.31, p = .0024). In the PGC-ADHD dataset (using pooled data of cADHD and adults) tendency of associations were observed only among females with OR = 1.09 (1.02-1.17) for LRP5 rs3736228 and OR = 1.18 (1.09-1.25) for LRP6 rs2302685. Together, our findings suggest a potential sex-specific link of cADHD with LRP5 and LRP6 gene variants, which could contribute to the differences in brain maturation alterations in ADHD affected boys and girls, and suggest possible therapy targets.

Identifiants

DOI: 10.1002/ajmg.b.32695 PMID: 30474181 PMC: PMC6767385
pubmed: 30474181
doi: 10.1002/ajmg.b.32695
pmc: PMC6767385
doi:

Substances chimiques

LRP5 protein, human 0
LRP6 protein, human 0
Low Density Lipoprotein Receptor-Related Protein-5 0
Low Density Lipoprotein Receptor-Related Protein-6 0

Types de publication

Journal Article Meta-Analysis Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

365-376

Subventions

Organisme : Hungarian Brain Research Program
ID : NAP-B KTIA_NAP_13-2014-0011
Pays : International
Organisme : University of Zurich, Filling the Gap
ID : Postdoctoral to Anna Maria Werling
Pays : International
Organisme : University of Zurich
Pays : International
Organisme : Deutsche Forschungsgemeinschaft
ID : HE1446/9-1HI865/2-1KFO125
Pays : International

Informations de copyright

© 2018 The Authors. American Journal of Medical Genetics Part B: Neuropsychiatric Genetics published by Wiley Periodicals, Inc.

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Auteurs

Edna Grünblatt (E)

Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.
ORCID: 0000-0001-8505-7265

Zsofia Nemoda (Z)

Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.
Molecular Psychiatry Research Group, MTA-SE NAP-B, Hungarian Academy of Sciences, Budapest, Hungary.

Anna Maria Werling (AM)

Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.

Alexander Roth (A)

Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.

Nora Angyal (N)

Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry, Semmelweis University, Budapest, Hungary.

Zsanett Tarnok (Z)

Vadaskert Child and Adolescent Psychiatric Hospital, Budapest, Hungary.

Hauke Thomsen (H)

Division of Molecular Genetic Epidemiology (C050), German Cancer Research Center (DKFZ), Heidelberg, Germany.

Triinu Peters (T)

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.

Anke Hinney (A)

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.

Johannes Hebebrand (J)

Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University of Duisburg-Essen, University Hospital Essen, Essen, Germany.

Klaus-Peter Lesch (KP)

Division of Molecular Psychiatry, Center of Mental Health, University of Wuezburg, Wuerzburg, Germany.
Laboratory of Psychiatric Neurobiology, Institute of Molecular Medicine, I. M. Sechenov First Moscow State Medical University, Moscow, Russia.
Department of Neuroscience, School of Mental Health and Neuroscience, Maastricht University, Maastricht, The Netherlands.

Marcel Romanos (M)

Center of Mental Health, Department of Child and Adolescent Psychiatry, Psychosomatics and Psychotherapy, University Hospital of Wuerzburg, Wuerzburg, Germany.

Susanne Walitza (S)

Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland.
Neuroscience Center Zurich, University of Zurich and ETH Zurich, Zurich, Switzerland.
Zurich Center for Integrative Human Physiology, University of Zurich, Zurich, Switzerland.

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Classifications MeSH

questionsmedicales.fr › Personnes › Tranches d'âge › Adolescent › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Personnes › Tranches d'âge › Adulte › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Troubles mentaux › Troubles du développement neurologique › Troubles déficitaires de l'attention et du comportement perturbateur › Trouble déficitaire de l'attention avec hyperactivité › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Personnes › Tranches d'âge › Enfant › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Phénomènes génétiques › Variation génétique › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Eucaryotes › Animaux › Chordés › Vertébrés › Mammifères › Eutheria › Primates › Haplorhini › Catarrhini › Hominidae › Humains › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs Wnt › Protéine-5 apparentée au récepteur des LDL › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Acides aminés, peptides et protéines › Protéines › Protéines membranaires › Récepteurs de surface cellulaire › Récepteurs Wnt › Protéine-6 apparentée au récepteur des LDL › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Phénomènes physiologiques des appareils urinaire et reproducteur › Phénomènes physiologiques de la reproduction › Caractères sexuels › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Environnement et santé publique › Santé publique › Facteurs épidémiologiques › Facteurs sexuels › The involvement of the canonical Wnt-signaling...
questionsmedicales.fr › Phénomènes physiologiques cellulaires › Transduction du signal › Voie de signalisation Wnt › The involvement of the canonical Wnt-signaling...