Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study

Genes Brain Behav. 2011 Mar;10(2):149-57. doi: 10.1111/j.1601-183X.2010.00649.x. Epub 2010 Nov 4.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Attention Deficit Disorder with Hyperactivity / epidemiology*
  • Attention Deficit Disorder with Hyperactivity / genetics*
  • Case-Control Studies
  • DNA / genetics
  • DNA / isolation & purification
  • Diagnostic and Statistical Manual of Mental Disorders
  • Female
  • Genetic Markers
  • Genetic Predisposition to Disease / epidemiology*
  • Genotype
  • Haplotypes
  • Humans
  • Linkage Disequilibrium
  • Male
  • Neuropsychological Tests
  • Polymorphism, Single Nucleotide
  • Quality Control
  • Receptors, G-Protein-Coupled / genetics*
  • Receptors, Peptide / genetics*
  • Spain / epidemiology


  • ADGRL3 protein, human
  • Genetic Markers
  • Receptors, G-Protein-Coupled
  • Receptors, Peptide
  • DNA