PhD Scientific Days 2018

Oral presentations: Mental Sciences

Genetic association analysis of the canonical Wnt-signaling receptor genes LRP5 and LRP6 with Attention Deficit Hyperactivity Disorder

Előadó neve

Angyal, Nóra

Előadó munkahelye

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

Előadó telefonszáma

+36 1 459 15 00 / 60128

Előadó e-mail címe

angyal.nora@med.semmelweis-univ.hu

Az előadás címe

Genetic association analysis of the canonical Wnt-signaling receptor genes LRP5 and LRP6 with Attention Deficit Hyperactivity Disorder

Szerző(k) neve és munkahelye

Nora Angyal1, Zsanett Tarnok2, Edna Grunblatt3, János Réthelyi4,5, Zsofia Nemoda1,5
1 Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry,
Semmelweis University, Budapest, Hungary
2 Vadaskert Child and Adolescent Psychiatric Clinic, Budapest, Hungary
3 Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
4 Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary
5 Molecular Psychiatry Research Group, MTA-SE NAP-B, Hungarian Academy of Sciences, Budapest, Hungary

Bemutatás módja

Szóbeli

Szekció

Oral presentations: Mental Sciences

Language of the presentation

Hungarian

Témacsoport

mental health sciences

Összefoglaló szövege

Introduction: Attention Deficit Hyperactivity Disorder (ADHD) is one of the most common childhood-onset psychiatric disorders, showing high heritability estimates. In this complex inheritance disorder possibly multiple genetic and environmental factors act together during brain development to create a neurobiological susceptibility, similarly to other neurodevelopmental disorders, such as autism spectrum disorders. Altered Wnt-signaling, particularly the lipoprotein receptor-related protein 5 (LRP5) and LRP6 co-receptors, were linked to these disorders. Based on the hypothesis that Wnt-signaling can be involved in the pathogenesis of ADHD, a Swiss workgroup investigated, and found association between LRP5 and LRP6 genes and childhood-onset ADHD.
Aims: Replicate the genetic association of the LRP5 and LRP6 polymorphisms in Hungarian ADHD samples (pediatric and adult) using ADHD diagnosis, as well as symptom severity scores.
Methods: Two single nucleotide polymorphisms (rs4988319 and rs3736228 SNPs) were studied in the LRP5 and two SNPs (rs1012672, rs2302685) in the LRP6 gene. Our case-control study consisted of 191 ADHD children and 267 control subjects. A meta-analysis was performed including Swiss, German and Hungarian pediatric samples. In the dimensional analyses the hyperactivity, impulsivity, and inattention scores of ADHD-Rating Scales collected from 160 ADHD children and 95 adults were analyzed.
Results: In our case-control association study only tendentious association was found between LRP6 rs2302685 and ADHD (p=0.09). Since similar associations could be observed in other European samples, a meta-analysis was conducted, which showed a significant association of the LRP6 rs2302685 with pediatric ADHD (OR=1.21, 95% CI 1.03-1.41; p=0.02). Our dimensional analysis also showed association between LRP6 rs2302685 and ADHD inattention symptom score among children and adults (p=0.04, and 0.03, respectively).
Conclusion: Our findings suggest that a non-synonymous polymorphism (Val1062Ile) of the LRP6 gene is associated with attention problems, which points to the involvement of Wnt-signaling in the pathogenesis of ADHD.
Acknowledgment: The study was supported by KTIA_NAP_13-2014-0011.

Data of the presenter

Doctoral School of Molecular Medicine
Program: Pathobiochemistry
Supervisor: Zsófia Nemoda
E-mail address of the presenter: angyal.nora@med.semmelweis-univ.hu
E-mail address of the supervisor: nemoda.zsofia@med.semmelweis-univ.hu

Kind

Szabad

Status

elfogadva

Accepted presentation method

szóbeli

Előadás fájl jóváhagyás

nem rendelkezett róla

Előadó

2699

Authors (legacy)

Nora Angyal1, Zsanett Tarnok2, Edna Grunblatt3, János Réthelyi4,5, Zsofia Nemoda1,5
1 Institute of Medical Chemistry, Molecular Biology and Pathobiochemistry,
Semmelweis University, Budapest, Hungary
2 Vadaskert Child and Adolescent Psychiatric Clinic, Budapest, Hungary
3 Department of Child and Adolescent Psychiatry and Psychotherapy, University Hospital of Psychiatry Zurich, University of Zurich, Zurich, Switzerland
4 Department of Psychiatry and Psychotherapy, Semmelweis University, Budapest, Hungary
5 Molecular Psychiatry Research Group, MTA-SE NAP-B, Hungarian Academy of Sciences, Budapest, Hungary