This Article  • Full text  • PDF  • Reply to article  • Send to a friend  • Save in My Folder  • Save to citation manager  • Permissions  Citing Articles  • Contact me when this article is cited  Related Content  • Related letter  • Related article  • Similar articles in this journal  Topic Collections  • Substance Abuse/ Alcoholism  • Genetics  • Genetic Counseling/ Testing/ Therapy  • Statistics and Research Methods  • Public Health  • Alert me on articles by topic

	Since this article does not have an abstract, we have provided the first 150 words of the full text and any section headings.

We are concerned that the results appearing to implicate an effect of DRD2 polymorphisms on the susceptibility to heroin dependence¹ may represent statistical artifacts rather than a true genetic effect. To a very large extent, the results are based on estimating the frequencies of haplotypes in cases and controls and testing for a difference, the frequencies being estimated using the MLOCUS program.² Likelihood ratio tests assuming a ² distribution were reported to produce P values as low as 10^–10. A Fisher exact test for 1 haplotype produced a P value of 10^–22.

In case-control studies, haplotypes are not observed directly and their frequencies are only estimated. The authors of the MLOCUS program wrote that the use of the ² distribution could lead to an inflated type I error rate and hence recommended using resampling methods to obtain statistical significance.² Apparently minor errors in the estimation of haplotype frequency can yield . . . [Full Text of this Article]

AUTHOR INFORMATION
David Curtis, MD, PhD; Hugh Gurling, MD, MPhil, FRCPsych

RELATED LETTER

Estimation of Haplotypes at DRD2 May Have Produced Misleading Results—Reply
Ke Xu, Dirk Lichtermann, Robert H. Lipsky, Petra Franke, Xiehe Liu, Ying Hu, Liping Cao, Sibylle G. Schwab, Dieter B. Wildenauer, Claiton H. D. Bau, Erica Ferro, Will Astor, Thembi Finch, Jeanietta Terry, Julie Taubman, Wolfgang Maier, and David Goldman
Arch Gen Psychiatry. 2006;63(8):939-940.
EXTRACT | FULL TEXT  

RELATED ARTICLE

Association of Specific Haplotypes of D₂ Dopamine Receptor Gene With Vulnerability to Heroin Dependence in 2 Distinct Populations
Ke Xu, Dirk Lichtermann, Robert H. Lipsky, Petra Franke, Xiehe Liu, Ying Hu, Liping Cao, Sibylle G. Schwab, Dieter B. Wildenauer, Claiton H. D. Bau, Erica Ferro, Will Astor, Thembi Finch, Jeanietta Terry, Julie Taubman, Wolfgang Maier, and David Goldman
Arch Gen Psychiatry. 2004;61(6):597-606.
ABSTRACT | FULL TEXT