You are seeing this message because your Web browser does not support basic Web standards. Find out more about why this message is appearing and what you can do to make your experience on this site better.


ABOUT JAMA
Advanced Search

Welcome   | My Account | E-mail Alerts | Access Rights | Sign In


  Vol. 269 No. 13, April 7, 1993 TABLE OF CONTENTS
  JAMA
  •  Online Features
  Review
 This Article
 •References
 •Full text PDF
 •Send to a friend
 • Save in My Folder
 •Save to citation manager
 •Permissions
 Citing Articles
 •Citation map
 •Citing articles on HighWire
 •Contact me when this article is cited
 Related Content
 •Similar articles in JAMA
 Social Bookmarking
  Add to CiteULike Add to Connotea Add to Del.icio.us Add to Digg Add to Reddit Add to Technorati Add to Twitter What's this?

The A1 Allele at the D2 Dopamine Receptor Gene and Alcoholism

A Reappraisal

Joel Gelernter, MD; David Goldman, MD; Neil Risch, PhD

JAMA. 1993;269(13):1673-1677.


Abstract

Objective.
—An allelic association between the Taq I "A" system A1 allele at the D2 dopamine receptor locus (DRD2) and either alcoholism or severe alcoholism has been proposed. Our purpose was to evaluate whether, based on all of the accumulated evidence, this association could be considered to be proven.

Data Sources.
—We considered data from all published reports of DRD2 allele frequency in alcoholics, controls, or both.

Study Selection.
—We concentrated on the issue of replication. We therefore considered all data reported (on white samples, because DRD2 allele frequency varies by race and ethnicity) since the first report by Blum et al in 1990.

Data Synthesis.
—We analyzed the set of data for differences in allele frequencies between alcoholics and controls, and for heterogeneity among samples. We also investigated the influence of the data from the first group to report an association (including a subsequent report from that group) on the findings. Our analysis shows that, when all studies subsequent to the original study are considered, there is no significant difference in DRD2 A1 allele frequency between alcoholics and controls, there is significant heterogeneity among reported alcoholics and reported controls, and there is no significant difference in DRD2 A1 allele frequency between severe and not severe alcoholics. Also, the two reports of Blum et al account for all of the (nonsignificant) differences seen between controls, alcoholics, and severe alcoholics.

Conclusions.
—In general, heterogeneity among studies (for alcoholics or controls) is considerably greater than differences between alcoholics and controls overall. The findings to date can best be explained by more conservative interpretations than a confirmed physiologically important allelic association between DRD2 alleles and alcoholism. These other possibilities include sampling error and ethnic variation in those studies that individually showed a large effect.

(JAMA. 1993;269:1673-1677)



Author Affiliations

From the Yale University School of Medicine Departments of Psychiatry (Dr Gelernter), Epidemiology and Public Health (Dr Risch), and Genetics (Dr Risch), New Haven, Conn; West Haven (Conn) Department of Veterans Affairs Medical Center (Dr Gelernter); and Laboratory of Neurogenetics, National Institute on Alcohol Abuse and Alcoholism, Bethesda, Md (Dr Goldman).


Footnotes

Reprint requests to Psychiatry 116A, West Haven Department of Veterans Affairs Medical Center, 950 Campbell Ave, West Haven, CT 06516 (Dr Gelernter).



Add to CiteULike CiteULike   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter     What's this?

THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES

All in the Family: Gene x Environment Interaction Between DRD2 and Criminal Father Is Associated With Five Antisocial Phenotypes
DeLisi et al.
Criminal Justice and Behavior 2009;36:1187-1197.
ABSTRACT  

Dopamine D2 Receptor Genotype Is Associated with Increased Mortality at a 10-Year Follow-up of Alcohol-Dependent Individuals
Berggren et al.
Alcohol Alcohol 2009;0:agp041v1-agp041.
ABSTRACT | FULL TEXT  

STrengthening the REporting of Genetic Association Studies (STREGA): An Extension of the STROBE Statement
Little et al.
ANN INTERN MED 2009;150:206-215.
ABSTRACT | FULL TEXT  

Meta-Analysis of the Association of the Taq1A Polymorphism with the Risk of Alcohol Dependency: A HuGE Gene-Disease Association Review
Smith et al.
Am J Epidemiol 2008;167:125-138.
ABSTRACT | FULL TEXT  

Association of haplotypic variants in DRD2, ANKK1, TTC12 and NCAM1 to alcohol dependence in independent case control and family samples
Yang et al.
Hum Mol Genet 2007;16:2844-2853.
ABSTRACT | FULL TEXT  

Haplotype spanning TTC12 and ANKK1, flanked by the DRD2 and NCAM1 loci, is strongly associated to nicotine dependence in two distinct American populations
Gelernter et al.
Hum Mol Genet 2006;15:3498-3507.
ABSTRACT | FULL TEXT  

Association of Specific Haplotypes of D2 Dopamine Receptor Gene With Vulnerability to Heroin Dependence in 2 Distinct Populations
Xu et al.
Arch Gen Psychiatry 2004;61:597-606.
ABSTRACT | FULL TEXT  

Nonreplication in Genetic Association Studies of Obesity and Diabetes Research
Redden and Allison
J. Nutr. 2003;133:3323-3326.
ABSTRACT | FULL TEXT  

Synonymous mutations in the human dopamine receptor D2 (DRD2) affect mRNA stability and synthesis of the receptor
Duan et al.
Hum Mol Genet 2003;12:205-216.
ABSTRACT | FULL TEXT  

Reporting, Appraising, and Integrating Data on Genotype Prevalence and Gene-Disease Associations
Little et al.
Am J Epidemiol 2002;156:300-310.
ABSTRACT | FULL TEXT  

Point: Population Stratification: A Problem for Case-Control Studies of Candidate-Gene Associations?
Thomas and Witte
Cancer Epidemiol. Biomarkers Prev. 2002;11:505-512.
FULL TEXT  

Evolution of genetic analysis strategies in coronary heart disease: a case of unnatural selection?
Keavney and Watkins
Eur Heart J 2001;22:271-273.
 

Population Admixture: Detection by Hardy-Weinberg Test and Its Quantitative Effects on Linkage-Disequilibrium Methods for Localizing Genes Underlying Complex Traits
Deng et al.
Genetics 2001;157:885-897.
ABSTRACT | FULL TEXT  

Population Stratification in Epidemiologic Studies of Common Genetic Variants and Cancer: Quantification of Bias
Wacholder et al.
JNCI J Natl Cancer Inst 2000;92:1151-1158.
ABSTRACT | FULL TEXT  

Neuropsychological Function, Drug Abuse, and Violence: A Conceptual Framework
FISHBEIN
Criminal Justice and Behavior 2000;27:139-159.
ABSTRACT  

Design of Gene Characterization Studies: an Overview
Thomas
J Natl Cancer Inst Monogr 1999;1999:17-23.
ABSTRACT | FULL TEXT  

TRAIT MARKERS FOR ALCOHOLISM: CLINICAL UTILITY
Farren and Tipton
Alcohol Alcohol 1999;34:649-665.
ABSTRACT | FULL TEXT  

Clinical Epidemiological Quality in Molecular Genetic Research: The Need for Methodological Standards
Bogardus et al.
JAMA 1999;281:1919-1926.
ABSTRACT | FULL TEXT  

A Tryptophan Hydroxylase Gene Marker for Suicidality and Alcoholism
Nielsen et al.
Arch Gen Psychiatry 1998;55:593-602.
ABSTRACT | FULL TEXT  

Genetic Polymorphisms and Disease
Altshuler et al.
NEJM 1998;338:1626-1626.
FULL TEXT  

Modification of Alcohol Withdrawal by the A9 Allele of the Dopamine Transporter Gene
Schmidt et al.
Am. J. Psychiatry 1998;155:474-478.
ABSTRACT | FULL TEXT  

Fatty acid ethyl esters: short-term and long-term serum markers of ethanol intake
Laposata
Clin. Chem. 1997;43:1527-1534.
ABSTRACT | FULL TEXT  

Dopamine D2 Receptor and Tourette's Syndrome
Comings
Arch Neurol 1995;52:441-442.
ABSTRACT  

Allelic Variation in the D4 Dopamine Receptor (DRD4) Gene Does Not Predict Response to Clozapine
Rao et al.
Arch Gen Psychiatry 1994;51:912-917.
ABSTRACT  

D2 Dopamine Receptor Alleles Do Not Influence Severity of Tourette's Syndrome: Results From Four Large Kindreds
Gelernter et al.
Arch Neurol 1994;51:397-400.
ABSTRACT  

No Structural Mutation in the Dopamine D2 Receptor Gene in Alcoholism or Schizophrenia: Analysis Using Denaturing Gradient Gel Electrophoresis
Gejman et al.
JAMA 1994;271:204-208.
ABSTRACT  

Alcoholism and the D2 Dopamine Receptor Gene
Noble and Blum
JAMA 1993;270:1547-1547.
ABSTRACT  

Alcoholism and the D2 Dopamine Receptor Gene-Reply
Gelernter et al.
JAMA 1993;270:1547-1548.
ABSTRACT  





HOME | CURRENT ISSUE | PAST ISSUES | TOPIC COLLECTIONS | CME | SUBMIT | SUBSCRIBE | HELP
CONDITIONS OF USE | PRIVACY POLICY | CONTACT US | SITE MAP
 
© 1993 American Medical Association. All Rights Reserved.