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

Neuromolecular Med. 2019 Mar;21(1):60-67. doi: 10.1007/s12017-019-08525-x. Epub 2019 Jan 16.

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: ADGRL3; ADHD; ASD; LPHN3; Neurodevelopment; Sex-specific effects.

MeSH terms

  • Adolescent
  • Adult
  • Age Distribution
  • Age of Onset
  • Attention Deficit Disorder with Hyperactivity / epidemiology
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Autism Spectrum Disorder / epidemiology
  • Autism Spectrum Disorder / genetics*
  • Brain / embryology
  • Brain / metabolism
  • Child
  • Computer Simulation
  • Gene Expression Regulation, Developmental
  • Genetic Predisposition to Disease
  • Humans
  • Male
  • Models, Genetic
  • Nerve Tissue Proteins / biosynthesis
  • Nerve Tissue Proteins / genetics*
  • Nerve Tissue Proteins / physiology
  • Neurodevelopmental Disorders / epidemiology
  • Neurodevelopmental Disorders / genetics
  • Polymorphism, Single Nucleotide*
  • Receptors, G-Protein-Coupled / biosynthesis
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, G-Protein-Coupled / physiology
  • Receptors, Peptide / biosynthesis
  • Receptors, Peptide / genetics*
  • Receptors, Peptide / physiology
  • Sex Distribution
  • Young Adult

Substances

  • ADGRL3 protein, human
  • Nerve Tissue Proteins
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide