A powerful likelihood method for the analysis of linkage disequilibrium between trait loci and one or more polymorphic marker loci

Journal Article · Wed Mar 01 04:00:00 EST 1995 · American Journal of Human Genetics

OSTI ID:70450

Terwilliger, J D ^[1]

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1. Univ. of Oxford (United Kingdom)

Historically, most methods for detecting linkage disequilibrium were designed for use with diallelic marker loci, for which the analysis is straightforward. With the advent of polymorphic markers with many alleles, the normal approach to their analysis has been either to extend the methodology for two-allele systems (leading to an increase in df and to a corresponding loss of power) or to select the allele believed to be associated and then collapse the other alleles, reducing, in a biased way, the locus to a diallelic system. I propose a likelihood-based approach to testing for linkage disequilibrium, an approach that becomes more conservative as the number of alleles increases, and as the number of markers considered jointly increases in a multipoint test for linkage disequilibrium, while maintaining high power. Properties of this method for detecting associations and fine mapping the location of disease traits are investigated. It is found to be, in general, more powerful than conventional methods, and it provides a tractable framework for the fine mapping of new disease loci. Application to the cystic fibrosis data of Kerem et al. is included to illustrate the method. 12 refs., 4 figs., 4 tabs.

• OSTI ID: 70450
• Journal Information: American Journal of Human Genetics, Journal Name: American Journal of Human Genetics Journal Issue: 3 Vol. 56; ISSN AJHGAG; ISSN 0002-9297
• Country of Publication: United States
• Language: English

Related Subjects

55 BIOLOGY AND MEDICINE
BASIC STUDIES
99 GENERAL AND MISCELLANEOUS
CALCULATION METHODS
COMPUTER CODES
GENES
GENETIC MAPPING
HUMAN CHROMOSOMES
STATISTICAL MODELS