Hum Hered 2006;61:144–156

Thermometers: Something for Statistical Geneticists to Think about

Vieland V.J.
College of Public Health and Carver College of Medicine, University of Iowa, Iowa City, Iowa, USA
email Corresponding Author

 goto top of outline Key Words

  • Statistical evidence
  • Measurement
  • LODs
  • p values
  • PPL

 goto top of outline Abstract

In human genetics, we measure the strength of statistical evidence using a variety of maximized likelihood ratios, LODs, and empirical p values. I argue here that these statistics have highly undesirable properties as evidence measures when applied to complex disorders. Among other deficiencies, I show that when following up on an interesting finding, they will tend to erroneously indicate diminished evidence as more data are considered (e.g., the LOD will tend to go down at a linked locus as the sample size increases). This violates a fundamental assumption underlying standard linkage and association designs in which we first scan the genome for our best signals, and then follow up at those genomic positions with additional data. I argue here for a coherent theoretical approach to formalizing statistical evidence measures, and derive a set of minimal requirements that any evidence measure should meet, drawing heavily on an analogy with the thermometer. I speculate that measures of evidence that come closer to meeting these requirements will do a better job of finding and characterizing genes, and I propose an alternative evidence metric as a step in this direction.

Copyright © 2006 S. Karger AG, Basel

 goto top of outline References
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    External Resources

  16. Yang X, Huang J, Logue MW, Vieland VJ: The posterior probability of linkage allowing for linkage disequilibrium and a new estimate of disequilibrium between a trait and a marker. Human Hered 2005;59:210–219.
  17. Bartlett CW, Vieland VJ: Two novel quantitative trait linkage analysis statistics based on the posterior probability of linkage: Application to the COGA families. Biomed Central Genetics, in press.
  18. Logue MW, Vieland VJ: A new method for computing the multipoint posterior probability of linkage. Hum Hered 2004;57:90–99.
  19. Wang K, Huang J, Vieland VJ: The consistency of the posterior probability of linkage. Annals Hum Genet 2000;64(Pt 6):533–553.
  20. Elston RC, Lange K: An approximation for the prior probability of autosomal linkage. Cytogenetics & Cell Genetics 1975;14:290–292.

 goto top of outline Author Contacts

Prof. Veronica J. Vieland
Center for Statistical Genetics Research
2190 Westlawn Bldg., University of Iowa
Iowa City IA 52242-1008 (USA)
Tel. +1 319 353 4782, Fax +1 319 353 3038, E-Mail

 goto top of outline Article Information

Received: February 27, 2006
Accepted after revision: April 12, 2006
Published online: June 12, 2006
Number of Print Pages : 13
Number of Figures : 2, Number of Tables : 1, Number of References : 20

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 61, No. 3, Year 2006 (Cover Date: August 2006)

Journal Editor: Devoto, M. (Philadelphia, Pa.)
ISSN: 0001–5652 (print), 1423–0062 (Online)

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