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Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse.

Nikpay M, Šeda O, Tremblay J, Petrovich M, Gaudet D, Kotchen TA, Cowley AW, Hamet P - Hypertens. Res. (2012)

Bottom Line: To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58,000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures.Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives.In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche, Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada.

ABSTRACT
Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58,000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures. Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives. Genetic mappings uncovered numerous shared genes among substance use, stress response, obesity and hemodynamic traits, including CAMK4, CNTN4, DLG2, FHIT, GRID2, ITPR2, NOVA1 and PRKCE, forming network of interacting proteins, sharing synaptic function and display higher and patterned expression profiles in brain-related tissues; moreover, pathway analysis of shared genes pointed to long-term potentiation. Subgroup genetic mappings uncovered additional shared synaptic genes, including CAMK4, CNTN5 and DNM3 (hypertension-specific); CNTN4, DNM3, FHIT and ITPR1 (sex-specific), having protein interactions with genes driven from general analysis. In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences.

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Hypothetical model of the interaction between stress, synaptic plasticity, substance use, obesity and related cardiovascular outcomes. Stressors can change the efficacy of mental processes such as synaptic plasticity. However, other environmental factors, such as substance use, modify the sensitivity of synaptic plasticity to the stressors. In the long term, the combined effects of genetic variations in the synapses and environmental factors shape an individual's lifestyles and habits. Conversely, the established habits and lifestyle influence the body and eventually modify health status outcomes, including cardiovascular disease and cardiovascular risk factors phenotypes as obesity. Nonetheless, there are other factors that modify cardiovascular outcomes through different mechanisms. A full color version of this figure is available at the Hypertension Research journal online.
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fig4: Hypothetical model of the interaction between stress, synaptic plasticity, substance use, obesity and related cardiovascular outcomes. Stressors can change the efficacy of mental processes such as synaptic plasticity. However, other environmental factors, such as substance use, modify the sensitivity of synaptic plasticity to the stressors. In the long term, the combined effects of genetic variations in the synapses and environmental factors shape an individual's lifestyles and habits. Conversely, the established habits and lifestyle influence the body and eventually modify health status outcomes, including cardiovascular disease and cardiovascular risk factors phenotypes as obesity. Nonetheless, there are other factors that modify cardiovascular outcomes through different mechanisms. A full color version of this figure is available at the Hypertension Research journal online.

Mentions: On the basis of above findings, we propose a model that (Figure 4) once an environmental stressor is perceived at synapses, it can alter the efficacy of synaptic plasticity; however, other environmental factors as substance use can modify the sensitivity of synaptic plasticity to the stressors. In the long term, the combined effects of genetic variations in the synapses and environmental factors shape an individual's lifestyles and habits. Conversely, the established habits and lifestyle influence the body and eventually modify health status outcomes, including cardiovascular disease and cardiovascular risk factor phenotypes, such as obesity. Nonetheless, because different means can lead to the same end, other factors can influence the cardiovascular system through different mechanisms.


Genetic mapping of habitual substance use, obesity-related traits, responses to mental and physical stress, and heart rate and blood pressure measurements reveals shared genes that are overrepresented in the neural synapse.

Nikpay M, Šeda O, Tremblay J, Petrovich M, Gaudet D, Kotchen TA, Cowley AW, Hamet P - Hypertens. Res. (2012)

Hypothetical model of the interaction between stress, synaptic plasticity, substance use, obesity and related cardiovascular outcomes. Stressors can change the efficacy of mental processes such as synaptic plasticity. However, other environmental factors, such as substance use, modify the sensitivity of synaptic plasticity to the stressors. In the long term, the combined effects of genetic variations in the synapses and environmental factors shape an individual's lifestyles and habits. Conversely, the established habits and lifestyle influence the body and eventually modify health status outcomes, including cardiovascular disease and cardiovascular risk factors phenotypes as obesity. Nonetheless, there are other factors that modify cardiovascular outcomes through different mechanisms. A full color version of this figure is available at the Hypertension Research journal online.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3368234&req=5

fig4: Hypothetical model of the interaction between stress, synaptic plasticity, substance use, obesity and related cardiovascular outcomes. Stressors can change the efficacy of mental processes such as synaptic plasticity. However, other environmental factors, such as substance use, modify the sensitivity of synaptic plasticity to the stressors. In the long term, the combined effects of genetic variations in the synapses and environmental factors shape an individual's lifestyles and habits. Conversely, the established habits and lifestyle influence the body and eventually modify health status outcomes, including cardiovascular disease and cardiovascular risk factors phenotypes as obesity. Nonetheless, there are other factors that modify cardiovascular outcomes through different mechanisms. A full color version of this figure is available at the Hypertension Research journal online.
Mentions: On the basis of above findings, we propose a model that (Figure 4) once an environmental stressor is perceived at synapses, it can alter the efficacy of synaptic plasticity; however, other environmental factors as substance use can modify the sensitivity of synaptic plasticity to the stressors. In the long term, the combined effects of genetic variations in the synapses and environmental factors shape an individual's lifestyles and habits. Conversely, the established habits and lifestyle influence the body and eventually modify health status outcomes, including cardiovascular disease and cardiovascular risk factor phenotypes, such as obesity. Nonetheless, because different means can lead to the same end, other factors can influence the cardiovascular system through different mechanisms.

Bottom Line: To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58,000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures.Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives.In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences.

View Article: PubMed Central - PubMed

Affiliation: Centre de Recherche, Centre hospitalier de l'Université de Montréal, Montréal, Québec, Canada.

ABSTRACT
Links between substance use habits, obesity, stress and the related cardiovascular outcomes can be, in part, because of loci with pleiotropic effects. To investigate this hypothesis, we performed genome-wide mapping in 119 multigenerational families from a population in the Saguenay-Lac-St-Jean region with a known founder effect using 58,000 single-nucleotide polymorphisms and 437 microsatellite markers to identify genetic components of the following factors: habitual alcohol, tobacco and coffee use; response to mental and physical stress; obesity-related traits; and heart rate (HR) and blood pressure (BP) measures. Habitual alcohol and/or tobacco users had attenuated HR responses to mental stress compared with non-users, whereas hypertensive individuals had stronger HR and systolic BP responses to mental stress and a higher obesity index than normotensives. Genetic mappings uncovered numerous shared genes among substance use, stress response, obesity and hemodynamic traits, including CAMK4, CNTN4, DLG2, FHIT, GRID2, ITPR2, NOVA1 and PRKCE, forming network of interacting proteins, sharing synaptic function and display higher and patterned expression profiles in brain-related tissues; moreover, pathway analysis of shared genes pointed to long-term potentiation. Subgroup genetic mappings uncovered additional shared synaptic genes, including CAMK4, CNTN5 and DNM3 (hypertension-specific); CNTN4, DNM3, FHIT and ITPR1 (sex-specific), having protein interactions with genes driven from general analysis. In summary, consistent with the observed phenotypic correlations, we found substantial overlap among genomic determinants of these traits in synapse, which supports the notion that the neural synapse may be a shared interface behind substance use, stress, obesity, HR, BP as well as the observed sex- and hypertension-specific genetic differences.

Show MeSH
Related in: MedlinePlus