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A two-locus genetic interaction between LPHN3 and 11q predicts ADHD severity and long-term outcome.
Transl Psychiatry 2011; 1:e17TP

Abstract

The severity of attention-deficit/hyperactivity disorder (ADHD) symptoms is a major predictor of long-term ADHD outcome. To investigate if two-locus interactions might predict ADHD severity, we studied a sample of 1341 individuals from families clustering ADHD, using the Vanderbilt Assessment Scale for Parents. Latent class cluster analysis was used to construct symptom profiles and classify ADHD severity. Single nucleotide polymorphisms (SNPs) spanning ADHD-linked chromosomal regions on chromosomes 4, 5, 10, 11, 12 and 17 were genotyped. SNPs associated with ADHD severity were identified and potential two-locus genetic interactions were tested. We found that SNPs within the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 not only to increase the risk of developing ADHD but also to increase ADHD severity. All these genes are identified to have a major role in shaping both brain development and function. These findings demonstrate that genetic interactions may predict the severity of ADHD, which in turn may predict long-term ADHD outcome.

Authors+Show Affiliations

Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3717, USA.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Intramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

22832519

Citation

Acosta, M T., et al. "A Two-locus Genetic Interaction Between LPHN3 and 11q Predicts ADHD Severity and Long-term Outcome." Translational Psychiatry, vol. 1, 2011, pp. e17.
Acosta MT, Vélez JI, Bustamante ML, et al. A two-locus genetic interaction between LPHN3 and 11q predicts ADHD severity and long-term outcome. Transl Psychiatry. 2011;1:e17.
Acosta, M. T., Vélez, J. I., Bustamante, M. L., Balog, J. Z., Arcos-Burgos, M., & Muenke, M. (2011). A two-locus genetic interaction between LPHN3 and 11q predicts ADHD severity and long-term outcome. Translational Psychiatry, 1, pp. e17. doi:10.1038/tp.2011.14.
Acosta MT, et al. A Two-locus Genetic Interaction Between LPHN3 and 11q Predicts ADHD Severity and Long-term Outcome. Transl Psychiatry. 2011 Jul 5;1:e17. PubMed PMID: 22832519.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - A two-locus genetic interaction between LPHN3 and 11q predicts ADHD severity and long-term outcome. AU - Acosta,M T, AU - Vélez,J I, AU - Bustamante,M L, AU - Balog,J Z, AU - Arcos-Burgos,M, AU - Muenke,M, Y1 - 2011/07/05/ PY - 2012/7/27/entrez PY - 2011/1/1/pubmed PY - 2013/4/5/medline SP - e17 EP - e17 JF - Translational psychiatry JO - Transl Psychiatry VL - 1 N2 - The severity of attention-deficit/hyperactivity disorder (ADHD) symptoms is a major predictor of long-term ADHD outcome. To investigate if two-locus interactions might predict ADHD severity, we studied a sample of 1341 individuals from families clustering ADHD, using the Vanderbilt Assessment Scale for Parents. Latent class cluster analysis was used to construct symptom profiles and classify ADHD severity. Single nucleotide polymorphisms (SNPs) spanning ADHD-linked chromosomal regions on chromosomes 4, 5, 10, 11, 12 and 17 were genotyped. SNPs associated with ADHD severity were identified and potential two-locus genetic interactions were tested. We found that SNPs within the LPHN3 gene interact with SNPs spanning the 11q region that contains DRD2 and NCAM1 not only to increase the risk of developing ADHD but also to increase ADHD severity. All these genes are identified to have a major role in shaping both brain development and function. These findings demonstrate that genetic interactions may predict the severity of ADHD, which in turn may predict long-term ADHD outcome. SN - 2158-3188 UR - https://www.unboundmedicine.com/medline/citation/22832519/A_two_locus_genetic_interaction_between_LPHN3_and_11q_predicts_ADHD_severity_and_long_term_outcome_ L2 - http://dx.doi.org/10.1038/tp.2011.14 DB - PRIME DP - Unbound Medicine ER -