GENES, LOGIC AND STATISTICS: RESPONSE TO A REVIEW

M. M. Vanyukov

Center for Education and Drug Abuse Research, University of Pittsburgh, Pittsburgh, PA 15261, USA

Received 27 July 2001; accepted 31 August 2001

Buckland (2001) in his review classifies as ‘ludicrous’ my analysis of the Goldman et al. (1997) data (Vanyukov, 1999Go) and cites it as ‘[a]n example of statistics taking priority over logic’. The analysis suggests a possibility of the over-representation of homozygotes for a rare allele of a functional polymorphism in the DRD2 gene among substance abusers. Buckland's conclusion is based on his opinion that the frequencies of this genotype among substance abusers (0.055) and controls (0.022) cannot be compared because they ‘represent nine and six individuals respectively’. It should be noted, however, that the comparison is based as much on these numbers as on the much larger numbers in the other two cells of this 2 x 2 {chi}2 analysis, involving 170 affected and 267 non-affected individuals. Contrary to Buckland's opinion, this is a comparison of distributions, rather than two numbers. Moreover, as is commonly known, an analysis of this kind would be possible even with a smaller sample or with a number in a cell less than 5, as long as the proper test (Fisher's exact test) or correction (Yates's continuity correction) is applied. The standard test applied in my analysis is completely legitimate. Indeed, the analysis addresses the possibility of overlooking positive results when the statistical approach is formal, rather than based on logic and the biological meaning of the data. It is regrettable that an invited review in a respected journal such as Alcohol and Alcoholism does not exercise necessary caution in dismissing previously published results.

FOOTNOTES

Editor's note: Dr P. R. Buckland has read the above Letter to the Editors, but declined a response beyond his original statements. A.A.-B.B.

REFERENCES

Buckland, P. R. (2001) Genetic association studies of alcoholism — problems with the candidate gene approach. Alcohol and Alcoholism 36, 99–103.[Abstract/Free Full Text]

Goldman, D., Urbanec, M., Guenther, D., Robin, R. and Long, J. C. (1997) Linkage and association of a functional DRD2 variant [Ser311Cys] and DRD2 markers to alcoholism, substance abuse, and schizophrenia in Southwestern American Indians. American Journal of Medical Genetics 74, 386–394.[ISI][Medline]

Vanyukov, M. M. (1999) An association between a functional polymorphism at the DRD2 gene and the liability to substance abuse. American Journal of Medical Genetics 88, 446–447.[ISI][Medline]





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