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Permanent URL to this publication: http://dx.doi.org/10.5167/uzh-49845

Jain, Mahim; Vélez, Jorge I.; Acosta, Maria T.; Palacio, Louis Guillermo; Balog, Joan Z.; Roessler, Erich; Pineda, David A.; Londoño, Ana C.; Palacio, Juan Davis; Arbelaez, Andres; Lopera, Francisco; Elia, Josephine; Hakonarson, Hakon; Seitz, Christiane; Freitag, Christine M.; Palmason, Haukur; Meyer, Jobst; Romanos, Marcel; Walitza, Susanne; Hemminger, Uwe; Warnke, Andreas; Romanos, Jasmin; Renner, Tobias; Jacob, Christian P.; Lesch, Klaus-Peter; Swanson, James M.; Castellanos, Francisco Xavier; Bailey-Wilson, Joan E.; Arcos-Burgos, Mauricio; Muenke, Maximilian (2012). A cooperative interaction between LPHN3 and 11q doubles the risk for ADHD. Molecular Psychiatry, 17(7):741-747.

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Abstract

In previous studies of a genetic isolate, we identified significant linkage of attention deficit hyperactivity disorder (ADHD) to 4q, 5q, 8q, 11q and 17p. The existence of unique large size families linked to multiple regions, and the fact that these families came from an isolated population, we hypothesized that two-locus interaction contributions to ADHD were plausible. Several analytical models converged to show significant interaction between 4q and 11q (P<1 × 10(-8)) and 11q and 17p (P<1 × 10(-6)). As we have identified that common variants of the LPHN3 gene were responsible for the 4q linkage signal, we focused on 4q-11q interaction to determine that single-nucleotide polymorphisms (SNPs) harbored in the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 genes, to double the risk of developing ADHD. This interaction not only explains genetic effects much better than taking each of these loci effects by separated but also differences in brain metabolism as depicted by proton magnetic resonance spectroscopy data and pharmacogenetic response to stimulant medication. These findings not only add information about how high order genetic interactions might be implicated in conferring susceptibility to develop ADHD but also show that future studies of the effects of genetic interactions on ADHD clinical information will help to shape predictive models of individual outcome.

Item Type:Journal Article, refereed, original work
Communities & Collections:04 Faculty of Medicine > Center for Child and Adolescent Psychiatry
DDC:610 Medicine & health
Language:English
Date:2012
Deposited On:28 Sep 2011 14:35
Last Modified:27 Nov 2013 23:54
Publisher:Nature Publishing Group
ISSN:1359-4184
Publisher DOI:10.1038/mp.2011.59
PubMed ID:21606926
Citations:Web of Science®. Times Cited: 10
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