Articles, Essays, & Creative Writing

Document Type

Published Version

Publication Date

Spring 3-8-2023

Disciplines

Diseases | Genetics

Abstract

We propose a theoretical basis for analyzing several features of genetic diseases caused by dominant alleles, including: disease prevalence, genotype penetrance, and the relationship between causal genotype frequency and disease frequency. In addition, we provide a theoretical framework for accurate diagnosis and clinical approaches for disease study, including two examples in which inaccurate and incomplete diagnoses affect the estimates of disease prevalence: First, the disease iceberg effect shows that disease prevalence is often underestimated due to errors introduced by inaccurate diagnosis; second, because lifetime risk of disease is cumulative, and therefore an increasing function of age, measurements of prevalence are inaccurate if people of all ages are not included. Finally, we discuss the aggregation of genetic diseases. We identify theoretical and computational deficiencies associated with using the sibling recurrence-risk ratio as a measure of familial aggregation. We develop an alternative concept of aggregation and propose an associated measure that does not experience the deficiencies. Throughout, we provide clinicians and researchers practical implications of our theoretical framework.

Comments

This article is the publisher-created version, also considered to be the final version or the version of record. It includes value-added elements provided by the publisher, such as copy editing, layout changes, and branding consistent with the rest of the publication.

Rights

Creative Commons License
This work is licensed under a Creative Commons Attribution 4.0 License.

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