Tests and Estimates of Allelic Association in Complex Inheritance

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 1998 Sep 16

PMID 9736746

Citations 45

Authors

N E Morton

A Collins

Affiliations

Soon will be listed here.

Abstract

Family-based procedures such as the transmission disequilibrium test (TDT) were motivated by concern that sample-based methods to map disease genes by allelic association are not robust to population stratification, migration, and admixture. Other factors to consider in designing a study of allelic association are specification of gene action in a weakly parametric model, efficiency, diagnostic reliability for hypernormal individuals, interest in linkage and imprinting, and sibship composition. Family-based samples lend themselves to the TDT despite its inefficiency compared with cases and unrelated normal controls. The TDT has an efficiency of 1/2 for parent-offspring pairs and 2/3 for father-mother-child trios. Against cases and hypernormal controls, the efficiency is only 1/6 on the null hypothesis. Although dependent on marker gene frequency and other factors, efficiency for hypernormal controls is always greater than for random controls. Efficiency of the TDT is increased in multiplex families and by inclusion of normal sibs, approaching a case-control design with normal but not hypernormal controls. Isolated cases favor unrelated controls, and only in exceptional populations would avoidance of stratification justify a family-based design to map disease genes by allelic association.

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