Hum Hered 2004;58:131–138

Defining the Phenotype in Human Genetic Studies: Forward Genetics and Reverse Phenotyping

Schulze T.G.a,b · McMahon F.J.b
aDivision of Genetic Epidemiology in Psychiatry, Central Institute of Mental Health, University of Heidelberg, Mannheim, Germany; bGenetic Basis of Mood and Anxiety Disorders, Mood and Anxiety Program, National Institute of Mental Health, National Institutes of Health, Department of Health and Human Services, Bethesda,Md., USA
email Corresponding Author

 goto top of outline Key Words

  • Phenotypes
  • Assessment
  • Reliability
  • Validity
  • Covariate

 goto top of outline Abstract

The definition of phenotypes for genetic study is a challenging endeavor. Just as we apply strict quality standards to genotype data, we should expect that phenotypes meet consistently high standards of reproducibility and validity. The methods for achieving accurate phenotype assignment in the research setting – the ‘research diagnosis’ – are different from the methods used in clinical diagnosis in the patient care setting. We evaluate some of the main challenges of phenotype definition in human genetics, and begin to outline a set of standards to which phenotypes used in genetics studies may aspire with the goal of increasing the quality and reproducibility of linkage and association studies. Revisiting the traditional phenotype definitions through a focus on familial components and heritable endophenotypes is a time-honored approach. Reverse phenotyping, where phenotypes are refined based on genetic marker data, may be a promising new approach. The stakes are high, since the success of gene mapping in genetically complex disorders hinges on the ability to delineate the target phenotype with accuracy and precision.

Copyright © 2004 S. Karger AG, Basel

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 goto top of outline Author Contacts

Thomas G. Schulze, MD
Division of Genetic Epidemiology in Psychiatry
Central Institute of Mental Health, J5
D–68159 Mannheim (Germany)
Tel. +49 621 1703 6056, Fax +49 621 1703 6055, E-Mail

 goto top of outline Article Information

‘In writing the history of a disease, every philosophical hypothesis ... should lie in abeyance ... [T]he clear and natural phenomena of the disease should be noted ... accurately, and in all their minuteness; in imitation of the exquisite industry of those painters who represent in their portraits the smallest moles and faintest spots.’

Thomas Sydenham [1]

Number of Print Pages : 8
Number of Figures : 1, Number of Tables : 0, Number of References : 57

 goto top of outline Publication Details

Human Heredity (International Journal of Human and Medical Genetics)

Vol. 58, No. 3-4, Year 2004 (Cover Date: Released March 2005)

Journal Editor: J. Ott, New York, N.Y.
ISSN: 0001–5652 (print), 1423–0062 (Online)

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