The aggregate effect of dopamine genes on dependence symptoms among cocaine users: cross-validation of a candidate system scoring approach.

paper Primary Public

Authors: Derringer, Jaime; Krueger, Robert F; Dick, Danielle M; Aliev, Fazil; Grucza, Richard A; Saccone, Scott; Agrawal, Arpana; Edenberg, Howard J; Goate, Alison M; Hesselbrock, Victor M; Kramer, John R; Lin, Peng; Neuman, Rosalind J; Nurnberger, John I; Rice, John P; Tischfield, Jay A; GENEVA consortium; Bierut, Laura J
Year: 2012
Journal: Behavior genetics
PMID: 22358648
DOI: 10.1007/s10519-012-9531-4
PMCID: PMC3416038

#	Section	Preview
20	Results	Maximum variance explained in the testing sample was reached when the top four SNPs from the…
21	Results	from which the SNP weights were derived (p < 2.5 × 10−6). This same genetic risk score explained…
22	Results	The specificity of the genetic risk score was examined by correlating it with other substance…
23	Discussion	The current study sought to demonstrate a method of candidate system scoring in a sample that would…
24	Discussion	training sample by independently testing each SNP’s association with cocaine dependence symptoms,…
25	Discussion	Several of the four SNPs included in our genetic risk score have been previously investigated for…
26	Discussion	Also notable is the inclusion of rs1079597 (formerly known as DRD2 Taq1B) in the risk score.…
27	Discussion	Our cocaine-derived genetic risk score demonstrated specificity for cocaine dependence severity in…
28	Discussion — Limitations	The individuals included in the present analyses were not representative of the general population;…
29	Discussion — Limitations	Findings from genetic association studies such as the current analyses may be sensitive to the…
30	Discussion — Limitations	Our approach of selecting only SNPs located in genes known to be directly involved in a…
31	Discussion — Limitations	were unable to compare the results of the current limited-scope investigation to the results of a…
32	Discussion — Limitations	It is clear that our four-SNP score does not fully account for dopaminergic effects on cocaine…
33	Discussion — Conclusions	A risk score based upon four SNPs selected from a set of eight dopaminergic genes in an initial…
34	Discussion — Conclusions	Given our modest sample size, and substantial evidence implicating the dopamine system in cocaine…
35	Discussion — Conclusions	The cocaine-derived score identified within the current training sample predicted only cocaine…
36	Discussion — Conclusions	We detected four SNPs that in aggregate accounted for 0.55% of testing sample variance in cocaine…
37	Discussion — Conclusions	research and/or theoretical literature exists to allow for the a priori selection of a pathway for…

Name	Type
48bp VNTR in DRD4 local	variant
African	cohort
African American	cohort
age	phenotype
aggregate SNPs local	variant
alcohol	phenotype
alcohol dependence	phenotype
Alcohol Dependence Symptoms	phenotype
ANKK1	gene
behavioral response local	phenotype
borderline personality traits local	phenotype
brain glucose metabolism	phenotype
candidate SNP	cohort
cocaine	phenotype
Cocaine-based genetic risk score local	variant
Cocaine dependence symptom count local	phenotype
Cocaine-derived genetic risk score local	drug
Cocaine-derived SNP score local	variant
cocaine genetic risk score local	drug
Cocaine response local	phenotype
cocaine self-administration	phenotype
cocaine use disorder	phenotype
Cocaine Users Cohort local	cohort
COGEND	cohort
Collaborative Study on the Genetics of Alcoholism (COGA)	cohort
complex traits	phenotype
COMT	gene
conditioned place preference	phenotype
current sample	cohort
D1-like agonist local	drug
D2-like agonist local	drug
DBH	gene
DDC	gene
dependence symptom count local	phenotype
Detroit	cohort
diagnostic dichotomization local	phenotype
discovery sample	cohort
dopamine	drug
dopamine-related genes	gene
dopaminergic genes local	gene
Dopaminergic system	drug
Dopamine transporter	drug
DRD1	gene
DRD2	gene
DRD3	gene
DRD4	gene
DRD5	gene
drug-seeking behavior	phenotype
European ancestry	cohort
Family study of cocaine dependence	cohort
Four SNPs local	variant
four-SNP score local	variant
frequency or quantity of use local	phenotype
FSCD	cohort
genetic variants	cohort
heavy drinking	phenotype
Hispanic	phenotype
independent testing sample local	cohort
Independent testing sample local	cohort
informant- and self-report measures local	phenotype
initial training sample local	cohort
International schizophrenia Consortium	cohort
Liability to cocaine addiction local	phenotype
locomotion	phenotype
marijuana	phenotype
marijuana dependence	phenotype
marijuana dependence severity local	phenotype
Marijuana dependence symptom count local	phenotype
nicotine	drug
nicotine dependence	phenotype
Nicotine dependence symptom count local	phenotype
nicotine withdrawal	phenotype
non-Hispanic ancestry local	phenotype
nucleus accumbens	anatomy
original training sample local	cohort
PC1	phenotype
PC2	phenotype
prefrontal cortex	anatomy
problem use severity local	phenotype
propensity to use local	phenotype
R local	drug
replication testing sample local	cohort
risk score local	phenotype
rs1079597 local	variant
rs1611131 local	variant
rs1800497	variant
rs5326 local	variant
rs9817063 local	variant
SAGE	cohort
Saint Louis local	cohort
schizophrenia	phenotype
sex	phenotype
SLC6A3	gene
SLC6A3 knockout mice local	cohort
SNP	cohort
Spain	cohort
Study of Addiction: Genetics and Environment	cohort
Study source local	cohort
substance dependence symptom counts local	phenotype
substance-general genetic risk score local	phenotype
substance use	phenotype
substance use phenotypes	phenotype
tardive dyskinesia	phenotype
testing sample local	cohort
Testing sample local	cohort
tobacco dependence	phenotype
tobacco dependence severity local	phenotype
tobacco use	phenotype
Tourette syndrome	phenotype
training set	cohort

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