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August 2006, Vol 63, No. 8 >

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Letters to the Editor | August 2006

Estimation of Haplotypes at DRD2 May Have Produced Misleading Results

David Curtis, MD, PhD; Hugh Gurling, MD, MPhil, FRCPsych
Arch Gen Psychiatry. 2006;63(8):939. doi:10.1001/archpsyc.63.8.939-a.
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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 χ2 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.

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