Abstract:
:Attention-Deficit/Hyperactivity Disorder (ADHD) has a very high heritability (0.8), suggesting that about 80% of phenotypic variance is due to genetic factors. We used the integration of statistical and functional approaches to discover a novel gene that contributes to ADHD. For our statistical approach, we started with a linkage study based on large multigenerational families in a population isolate, followed by fine mapping of targeted regions using a family-based design. Family- and population-based association studies in five samples from disparate regions of the world were used for replication. Brain imaging studies were performed to evaluate gene function. The linkage study discovered a genome region harbored in the Latrophilin 3 gene (LPHN3). In the world-wide samples (total n=6360, with 2627 ADHD cases and 2531 controls) statistical association of LPHN3 and ADHD was confirmed. Functional studies revealed that LPHN3 variants are expressed in key brain regions related to attention and activity, affect metabolism in neural circuits implicated in ADHD, and are associated with response to stimulant medication. Linkage and replicated association of ADHD with a novel non-candidate gene (LPHN3) provide new insights into the genetics, neurobiology, and treatment of ADHD.
journal_name
Mol Psychiatryjournal_title
Molecular psychiatryauthors
Arcos-Burgos M,Jain M,Acosta MT,Shively S,Stanescu H,Wallis D,Domené S,Vélez JI,Karkera JD,Balog J,Berg K,Kleta R,Gahl WA,Roessler E,Long R,Lie J,Pineda D,Londoño AC,Palacio JD,Arbelaez A,Lopera F,Elia J,Hakondoi
10.1038/mp.2010.6subject
Has Abstractpub_date
2010-11-01 00:00:00pages
1053-66issue
11eissn
1359-4184issn
1476-5578pii
mp20106journal_volume
15pub_type
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journal_title:Molecular psychiatry
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