Using Patterns of Genetic Association to Elucidate Shared Genetic Etiologies Across Psychiatric Disorders.
Twin studies indicate that latent genetic factors overlap across comorbid psychiatric disorders. In this study, we used a novel approach to elucidate shared genetic factors across psychiatric outcomes by clustering single nucleotide polymorphisms based on their genome-wide association patterns. We applied latent profile analysis (LPA) to p-values resulting from genome-wide association studies across three phenotypes: symptom counts of alcohol dependence (AD), antisocial personality disorder (ASP), and major depression (MD), using the European-American case-control genome-wide association study subsample of the collaborative study on the genetics of alcoholism (N = 1399). In the 3-class model, classes were characterized by overall low associations (85.6% of SNPs), relatively stronger association only with MD (6.8%), and stronger associations with AD and ASP but not with MD (7.6%), respectively. These results parallel the genetic factor structure identified in twin studies. The findings suggest that applying LPA to association results across multiple disorders may be a promising approach to identify the specific genetic etiologies underlying shared genetic variance.
Department of Psychology, Virginia Commonwealth University, PO Box 842018, 817W. Franklin Street, Richmond, VA, 23284-2018, USA. sbcho@vcu.edu.|College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA. sbcho@vcu.edu.
Seung Bin
0000-0003-0336-6625
SB
Cho
Department of Psychology, Virginia Commonwealth University, PO Box 842018, 817W. Franklin Street, Richmond, VA, 23284-2018, USA.|College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA.|Faculty of Business, Karabuk University, Karabuk, Turkey.
Fazil
F
Aliev
Center for Biomarker Research and Precision Medicine, Virginia Commonwealth University, Richmond, VA, USA.
Shaunna L
SL
Clark
Department of Psychology, Virginia Commonwealth University, PO Box 842018, 817W. Franklin Street, Richmond, VA, 23284-2018, USA.|College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA.
Amy E
AE
Adkins
Department of Biochemistry and Molecular Biology, Indiana University School of Medicine, Indianapolis, IN, USA.
Howard J
HJ
Edenberg
Department of Psychiatry, Washington University, Saint Louis, MO, USA.
Kathleen K
KK
Bucholz
Department of Psychiatry and Behavioral Sciences, State University of New York Downstate Medical Center, Brooklyn, NY, USA.
Bernice
B
Porjesz
Department of Psychology, Virginia Commonwealth University, PO Box 842018, 817W. Franklin Street, Richmond, VA, 23284-2018, USA.|College Behavioral and Emotional Health Institute, Virginia Commonwealth University, Richmond, VA, USA.|Department of Human and Molecular Genetics, Virginia Commonwealth University, Richmond, VA, USA.
Danielle M
DM
Dick
D000437:Alcoholism / Q000235:genetics*; D000987:Antisocial Personality Disorder / Q000235:genetics*; D016022:Case-Control Studies; D016000:Cluster Analysis; D015897:Comorbidity; D003865:Major Depressive Disorder / Q000235:genetics*; D005260:Female; D056726:Genetic Association Studies / Q000379:methods* / Q000706:statistics & numerical data; D020022:Genetic Predisposition to Disease / Q000235:genetics; D014644:Genetic Variation / Q000235:genetics; D055106:Genome-Wide Association Study / Q000379:methods; D005838:Genotype; D006801:Humans; D008297:Male; D001523:Mental Disorders / Q000235:genetics; D008603:Mental Health; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D059467:Transcriptome / Q000235:genetics; D014429:Twins, Dizygotic / Q000235:genetics; D014430:Twins, Monozygotic / Q000235:genetics; D044465:White People / Q000235:genetics
Comorbidity; GWAS; Genetic etiology; Latent profile analysis; Psychiatric disorder