Genome-wide significant loci for addiction and anxiety.
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.



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.



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).



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.
Department of psychiatry, Yale University, School of Medicine, New Haven, CT, USA. Electronic address: karen.hodgson@yale.edu.
K
K
Hodgson
South Texas Diabetes and Obesity Institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA.
L
L
Almasy
Department of psychiatry, Yale University, School of Medicine, New Haven, CT, USA.
E E M
EE
Knowles
Department of Genetics, Texas Biomedical Research Institute, San Antonio, TX, USA.
J W
JW
Kent
South Texas Diabetes and Obesity Institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA.
J E
JE
Curran
South Texas Diabetes and Obesity Institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA.
T D
TD
Dyer
South Texas Diabetes and Obesity Institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA.
H H H
HH
Göring
Department of Psychiatry, University of Texas Health Science Center, San Antonio, TX, USA.
R L
RL
Olvera
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.
P T
PT
Fox
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.
G D
GD
Pearlson
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.
J H
JH
Krystal
South Texas Diabetes and Obesity Institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA.
R
R
Duggirala
South Texas Diabetes and Obesity Institute, University of Texas, Rio Grande Valley School of Medicine, Brownsville, TX, USA.
J
J
Blangero
Department of psychiatry, Yale University, School of Medicine, New Haven, CT, USA; Olin Neuropsychiatric Research Center, Institute of Living, Hartford Hospital, Hartford, CT, USA.
D C
DC
Glahn
D000328:Adult; D000437:Alcoholism / Q000235:genetics; D001008:Anxiety Disorders / Q000208:ethnology / Q000235:genetics*; D016739:Behavior, Addictive / Q000208:ethnology / Q000235:genetics*; D015897:Comorbidity; D005260:Female; D008040:Genetic Linkage; D006630:Hispanic or Latino / Q000706:statistics & numerical data*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010375:Pedigree; D010641:Phenotype; D019966:Substance-Related Disorders / Q000208:ethnology / Q000235:genetics*
Addiction; Anxiety; Comorbidity; Pleiotropy