The transmission/disequilibrium test: History, subdivision, and admixture

Journal Article · Tue Aug 01 04:00:00 EDT 1995 · American Journal of Human Genetics

OSTI ID:105253

Ewens, W J; Spielman, R S ^[1]

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1. Univ. of Pennsylvania, Philadelphia, PA (United States)

Disease association with a genetic marker is often taken as a preliminary indication of linkage with disease susceptibility. However, population subdivision and admixture may lead to diease association even in the absence of linkage. In a previous paper, we described a test for linkage (and linkage disequilibrium) between a genetic marker and disease susceptibility; linkage is detected by this test only if association is also present. This transmission/disequilibrium test (TDT) is carried out with data on transmission of marker alleles from parents heterozygous for the marker alleles to affected offspring. The TDT is a valid test for linkage and association, even when the association is caused by population subdivision and admixture. In the previous paper, we did not explicitly consider the effect of recent history on population structure. Here we extend the previous results by examining in detail the effects of subdivision and admixture, viewed as processes in population history. We describe two models for these processes. For both models, we analyze the properties of (a) the TDT as a test for linkage (and association) between marker and disease and (b) the conventional contingency statistic used with family data to test for population association. We show that the contingency test statistic does not have a {chi}{sup 2} distribution if subdivision or admixture is present. In contrast, the TDT remains a valid {chi}{sub 2} statistic for the linkage hypothesis, regardless of population history. 20 refs., 2 figs., 5 tabs.

• OSTI ID: 105253
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 2 Vol. 57; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
BIOLOGICAL MARKERS
BIOLOGICAL MODELS
GENES
GENETIC MAPPING
GENETICS
HEREDITARY DISEASES
HISTORICAL ASPECTS
HUMAN POPULATIONS
POPULATION DYNAMICS
STATISTICS