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Genome-wide significant loci for addiction and anxiety

Published online by Cambridge University Press:  23 March 2020

K. Hodgson ,
L. Almasy ,
E.E.M. Knowles ,
J.W. Kent ,
J.E. Curran ,
T.D. Dyer ,
H.H.H. Göring ,
R.L. Olvera ,
P.T. Fox  and
G.D. Pearlson
...Show all authors
K. Hodgson*
Affiliation:
Department of psychiatry, Yale University, School of Medicine, New Haven, CT, USA
L. Almasy
Affiliation:
South Texas Diabetes and Obesity institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA
E.E.M. Knowles
Affiliation:
Department of psychiatry, Yale University, School of Medicine, New Haven, CT, USA
J.W. Kent
Affiliation:
Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA
J.E. Curran
Affiliation:
South Texas Diabetes and Obesity institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA
T.D. Dyer
Affiliation:
South Texas Diabetes and Obesity institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA
H.H.H. Göring
Affiliation:
South Texas Diabetes and Obesity institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA
R.L. Olvera
Affiliation:
Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA
P.T. Fox
Affiliation:
Research Imaging Institute, University of Texas, Health Science Center, San Antonio, TX, USA South Texas Veterans Health System, 7400, Merton Minter, San Antonio, TX, USA
G.D. Pearlson
Affiliation:
Department of psychiatry, Yale University, School of Medicine, New Haven, CT, USA Olin Neuropsychiatric Research Center, Institute of Living, Hartford hospital, Hartford, CT, USA Department of Neurobiology, Yale University school of Medicine, New Haven, CT, USA
J.H. Krystal
Affiliation:
Department of psychiatry, Yale University, School of Medicine, New Haven, CT, USA Department of Neurobiology, Yale University school of Medicine, New Haven, CT, USA Clinical Neuroscience Division, VA National Center for PTSD, VA Connecticut Healthcare System, West Haven, CT, USA Psychiatry Services, Yale-New Haven Hospital, New Haven, CT, USA
R. Duggirala
Affiliation:
South Texas Diabetes and Obesity institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA
J. Blangero
Affiliation:
South Texas Diabetes and Obesity institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA
D.C. Glahn
Affiliation:
Department of psychiatry, Yale University, School of Medicine, New Haven, CT, USA Olin Neuropsychiatric Research Center, Institute of Living, Hartford hospital, Hartford, CT, USA
*
⁎Corresponding author. [email protected] Temple Medical Center, 40 Temple Street, 06510, New Haven, CT, USA.
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Abstract

Background

Psychiatric comorbidity is common among individuals with addictive disorders, with patients frequently suffering from anxiety disorders. While the genetic architecture of comorbid addictive and anxiety disorders remains unclear, elucidating the genes involved could provide important insights into the underlying etiology.

Methods

Here we examine a sample of 1284 Mexican-Americans from randomly selected extended pedigrees. Variance decomposition methods were used to examine the role of genetics in addiction phenotypes (lifetime history of alcohol dependence, drug dependence or chronic smoking) and various forms of clinically relevant anxiety. Genome-wide univariate and bivariate linkage scans were conducted to localize the chromosomal regions influencing these traits.

Results

Addiction phenotypes and anxiety were shown to be heritable and univariate genome-wide linkage scans revealed significant quantitative trait loci for drug dependence (14q13.2-q21.2, LOD = 3.322) and a broad anxiety phenotype (12q24.32-q24.33, LOD = 2.918). Significant positive genetic correlations were observed between anxiety and each of the addiction subtypes (ρg = 0.550–0.655) and further investigation with bivariate linkage analyses identified significant pleiotropic signals for alcohol dependence-anxiety (9q33.1-q33.2, LOD = 3.054) and drug dependence-anxiety (18p11.23-p11.22, LOD = 3.425).

Conclusions

This study confirms the shared genetic underpinnings of addiction and anxiety and identifies genomic loci involved in the etiology of these comorbid disorders. The linkage signal for anxiety on 12q24 spans the location of TMEM132D, an emerging gene of interest from previous GWAS of anxiety traits, whilst the bivariate linkage signal identified for anxiety-alcohol on 9q33 peak coincides with a region where rare CNVs have been associated with psychiatric disorders. Other signals identified implicate novel regions of the genome in addiction genetics.

Keywords

AddictionAnxietyComorbidityPleiotropy
Type
Original article
Information
European Psychiatry , Volume 36 , August 2016 , pp. 47 - 54
Copyright
Copyright © European Psychiatric Association 2016

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