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A common genetic network underlies substance use disorders and disruptive or externalizing disorders.

Arcos-Burgos M, Vélez JI, Solomon BD, Muenke M - Hum. Genet. (2012)

Bottom Line: Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors.Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment.We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented.

View Article: PubMed Central - PubMed

Affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3717, USA. arcosburgosm@mail.nih.gov

ABSTRACT
Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders.

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Related in: MedlinePlus

Linkage- and association-based genome scans identified loci containing common allelic variants contributing to SUD and to some psychiatric conditions
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Fig4: Linkage- and association-based genome scans identified loci containing common allelic variants contributing to SUD and to some psychiatric conditions

Mentions: Both linkage- and association-based genome scans have been conducted for specific drug dependencies as well as the vulnerability to addiction. While each study has identified many different loci, these data converge to likely represent true contributions of common allelic variants to polygenic models of genetic vulnerability to polysubstance abuse, and to some psychiatric conditions that share common manifestations (Fig. 4).Fig. 4


A common genetic network underlies substance use disorders and disruptive or externalizing disorders.

Arcos-Burgos M, Vélez JI, Solomon BD, Muenke M - Hum. Genet. (2012)

Linkage- and association-based genome scans identified loci containing common allelic variants contributing to SUD and to some psychiatric conditions
© Copyright Policy
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3351604&req=5

Fig4: Linkage- and association-based genome scans identified loci containing common allelic variants contributing to SUD and to some psychiatric conditions
Mentions: Both linkage- and association-based genome scans have been conducted for specific drug dependencies as well as the vulnerability to addiction. While each study has identified many different loci, these data converge to likely represent true contributions of common allelic variants to polygenic models of genetic vulnerability to polysubstance abuse, and to some psychiatric conditions that share common manifestations (Fig. 4).Fig. 4

Bottom Line: Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors.Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment.We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented.

View Article: PubMed Central - PubMed

Affiliation: Medical Genetics Branch, National Human Genome Research Institute, National Institutes of Health, Bethesda, MD 20892-3717, USA. arcosburgosm@mail.nih.gov

ABSTRACT
Here we summarize evidence obtained by our group during the last two decades, and contrasted it with a review of related data from the available literature to show that behavioral syndromes involving attention deficit/hyperactivity disorder (ADHD), externalizing disorders, and substance-use disorder (SUD) share similar signs and symptoms (i.e., have a biological basis as common syndromes), physiopathological and psychopathological mechanisms, and genetic factors. Furthermore, we will show that the same genetic variants harbored in different genes are associated with different syndromes and that non-linear interactions between genetic variants (epistasis) best explain phenotype severity, long-term outcome, and response to treatment. These data have been depicted in our studies by extended pedigrees, where ADHD, externalizing symptoms, and SUD segregate and co-segregate. Finally, we applied here a new formal network analysis using the set of significantly replicated genes that have been shown to be either associated and/or linked to ADHD, disruptive behaviors, and SUD in order to detect significantly enriched gene categories for protein and genetic interactions, pathways, co-expression, co-localization, and protein domain similarity. We found that networks related to pathways involved in axon guidance, regulation of synaptic transmission, and regulation of transmission of nerve impulse are overrepresented. In summary, we provide compiled evidence of complex networks of genotypes underlying a wide phenotype that involves SUD and externalizing disorders.

Show MeSH
Related in: MedlinePlus