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NeuroMolecular Medicine

, Volume 21, Issue 1, pp 60–67 | Cite as

ADGRL3 rs6551665 as a Common Vulnerability Factor Underlying Attention-Deficit/Hyperactivity Disorder and Autism Spectrum Disorder

  • Djenifer B. Kappel
  • Jaqueline B. Schuch
  • Diego L. Rovaris
  • Bruna S. da Silva
  • Diana Müller
  • Vitor Breda
  • Stefania P. Teche
  • Rudimar S. Riesgo
  • Lavínia Schüler-Faccini
  • Luís A. Rohde
  • Eugenio H. Grevet
  • Claiton H. D. BauEmail author
Original Paper
  • 99 Downloads

Abstract

Neurodevelopmental disorders are prevalent, frequently occur in comorbidity and share substantial genetic correlation. Previous evidence has suggested a role for the ADGRL3 gene in Attention-Deficit/Hyperactivity Disorder (ADHD) susceptibility in several samples. Considering ADGRL3 functionality in central nervous system development and its previous association with neurodevelopmental disorders, we aimed to assess ADGRL3 influence in early-onset ADHD (before 7 years of age) and Autism Spectrum Disorder (ASD). The sample comprises 187 men diagnosed with early-onset ADHD, 135 boys diagnosed with ASD and 468 male blood donors. We tested the association of an ADGRL3 variant (rs6551665) with both early-onset ADHD and ASD susceptibility. We observed significant associations between ADGRL3—rs6551665 on ADHD and ASD susceptibilities; we found that G-carriers were at increased risk of ADHD and ASD, in accordance with previous studies. The overall evidence from the literature, corroborated by our results, suggests that ADGRL3 might be involved in brain development, and genetic modifications related to it might be part of a shared vulnerability factor associated with the underlying neurobiology of neurodevelopmental disorders such as ADHD and ASD.

Keywords

ADHD ASD ADGRL3 LPHN3 Neurodevelopment Sex-specific effects 

Notes

Acknowledgements

We would like to thank the ProDAH-A team, the clinical staff at the Child Neurology Unit and all the individuals with ADHD, ASD and blood donors that participated in this study. We also thank Dr. Sandra Leistner-Segal at Medical Genetics Service from Hospital de Clínicas de Porto Alegre for the fragile X syndrome genotyping. This work received financial support from the Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq 424041/2016-2, 466722/2014-1, 476529/2012-3, and 484403/2007-9), Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES, AUX-PE-PROEX-1234/2011 and 376/2009) and Hospital de Clínicas de Porto Alegre (FIPE-HCPA 100358, 08543 and 05451).

Funding

The funding agencies were not involved in study design, data collection, analysis or interpretation of data, writing the report or in the decision to submit the article for publication.

Compliance with Ethical Standards

Conflict of interest

The author(s) declare the following potential conflict of interest with respect to the research, authorship and/or publication of this article: Dr. Grevet was on the speaker’s bureau for Novartis and Shire for the last 3 years. Dr. Rohde has received Honoraria, has been on the speakers’ bureau/advisory board and/or has acted as a consultant for Eli-Lilly, Janssen-Cilag, Medice, Novartis and Shire in the last three years. He receives authorship royalties from Oxford Press and ArtMed. The ADHD and Juvenile Bipolar Disorder Outpatient Programs chaired by him received unrestricted educational and research support from the following pharmaceutical companies in the last three years: Eli-Lilly, Janssen-Cilag, Novartis, and Shire. All other authors report no biomedical financial interests or potential conflicts of interest.

Ethical Approval

All procedures performed in studies involving human participants were in accordance with the ethical standards of the institutional and/or national research committee and with the 1964 Helsinki Declaration and its later amendments or comparable ethical standards.

Supplementary material

12017_2019_8525_MOESM1_ESM.pdf (119 kb)
Supplementary material 1 (PDF 118 KB)

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Copyright information

© Springer Science+Business Media, LLC, part of Springer Nature 2019

Authors and Affiliations

  • Djenifer B. Kappel
    • 1
    • 2
  • Jaqueline B. Schuch
    • 1
    • 2
    • 3
  • Diego L. Rovaris
    • 1
    • 2
  • Bruna S. da Silva
    • 1
    • 2
  • Diana Müller
    • 1
    • 2
  • Vitor Breda
    • 2
    • 4
  • Stefania P. Teche
    • 2
    • 4
  • Rudimar S. Riesgo
    • 5
  • Lavínia Schüler-Faccini
    • 1
  • Luís A. Rohde
    • 2
    • 4
    • 6
  • Eugenio H. Grevet
    • 2
    • 4
  • Claiton H. D. Bau
    • 1
    • 2
    Email author
  1. 1.Department of Genetics, Instituto de Biociências, Universidade Federal do Rio Grande do Sul, UFRGSPorto AlegreBrazil
  2. 2.ADHD Outpatient Program – Adult DivisionHospital de Clínicas de Porto AlegrePorto AlegreBrazil
  3. 3.Graduate Program in Biomedical GerontologyPontifícia Universidade Católica do Rio Grande do SulPorto AlegreBrazil
  4. 4.Department of Psychiatry, Faculdade de MedicinaUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  5. 5.Child Neurology Unit, Hospital de Clínicas de Porto AlegreUniversidade Federal do Rio Grande do SulPorto AlegreBrazil
  6. 6.National Institute of Developmental Psychiatry for Children and AdolescentsPorto AlegreBrazil

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