Contribution of LPHN3 to the genetic susceptibility to ADHD in adulthood: a replication study.
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.
Department of Psychiatry, Hospital Universitari Vall d'Hebron, Passeig Vall d'Hebron 119-129, Barcelona, Catalonia, Spain. mribases@ir.vhebron.net
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Ribasés
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Ramos-Quiroga
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Sánchez-Mora
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Bosch
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Richarte
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Palomar
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Gastaminza
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Bielsa
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Arcos-Burgos
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Muenke
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Castellanos
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Cormand
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Bayés
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D000328:Adult; D001289:Attention Deficit Disorder with Hyperactivity / Q000453:epidemiology* / Q000235:genetics*; D016022:Case-Control Studies; D004247:DNA / Q000235:genetics / Q000302:isolation & purification; D039721:Diagnostic and Statistical Manual of Mental Disorders; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000453:epidemiology*; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008297:Male; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide; D011786:Quality Control; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D018000:Receptors, Peptide / Q000235:genetics*; D013030:Spain / Q000453:epidemiology
C513284:ADGRL3 protein, human; D005819:Genetic Markers; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D004247:DNA