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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

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