Faculty Collaboration Database

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. Hypertens Res 2012 Jun;35(6):585-91

Date

02/03/2012

Pubmed ID

22297481

Pubmed Central ID

PMC3368234

DOI

10.1038/hr.2011.233

Scopus ID

2-s2.0-84861883171 (requires institutional sign-in at Scopus site)   34 Citations

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.

Author List

Nikpay M, Šeda O, Tremblay J, Petrovich M, Gaudet D, Kotchen TA, Cowley AW Jr, Hamet P

Author

Allen W. Cowley Jr PhD Professor in the Physiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Blood Pressure
Chromosome Mapping
Cohort Studies
Female
Gene Expression Regulation
Genome-Wide Association Study
Genotype
Heart Rate
Humans
Hypertension
Male
Microsatellite Repeats
Obesity
Phenotype
Polymorphism, Single Nucleotide
Sex Characteristics
Stress, Physiological
Stress, Psychological
Substance-Related Disorders
Synapses