Journal article
Linkage Detection Adaptive to Linkage Disequilibrium: The Disequilibrium Maximum-Likelihood–Binomial Test for Affected-Sibship Data
American journal of human genetics, Vol.65(6), pp.1741-1759
11/23/1999
DOI: 10.1086/302659
PMCID: PMC1288402
PMID: 10577929
Abstract
It has been demonstrated in the literature that the
transmission/disequilibrium test (TDT) has higher power than the
affected-sib-pair (ASP) mean test when linkage disequilibrium
(LD) is strong but that the mean test has higher power when LD is weak.
Thus, for ASP data, it seems clear that the TDT should be used when LD is
strong but that the mean test or other linkage tests should be used when LD
is weak or absent. However, in practice, it may be difficult to follow such
a guideline, because the extent of LD is often unknown. Even with a highly
dense genetic-marker map, in which some markers should be located
near the disease-predisposing mutation, strong LD is not inevitable.
Besides the genetic distance, LD is also affected by many factors, such as
the allelic heterogeneity at the disease locus, the initial LD, the allelic
frequencies at both disease locus and marker locus, and the age of the
mutation. Therefore, it is of interest to develop methods that are adaptive
to the extent of LD. In this report, we propose a disequilibrium
maximum-binomial-likelihood (DMLB) test that incorporates LD
in the maximum-binomial-likelihood (MLB) test. Examination of
the corresponding score statistics shows that this method adaptively
combines two sources of information: (
a
) the
identity-by-descent (IBD) sharing score, which is informative
for linkage regardless of the existence of LD, and (
b
) the
contrast between allele-specific IBD sharing score, which is
informative for linkage only in the presence of LD. For ASP data, the
proposed test has higher power than either the TDT or the mean test when
the extent of LD ranges from moderate to strong. Only when LD is very weak
or absent is the DMLB slightly less powerful than the mean test; in such
cases, the TDT has essentially no power to detect linkage. Therefore, the
DMLB test is an interesting approach to linkage detection when the extent
of LD is unknown.
Details
- Title: Subtitle
- Linkage Detection Adaptive to Linkage Disequilibrium: The Disequilibrium Maximum-Likelihood–Binomial Test for Affected-Sibship Data
- Creators
- Jian Huang - University of IowaYanming Jiang - University of Iowa
- Resource Type
- Journal article
- Publication Details
- American journal of human genetics, Vol.65(6), pp.1741-1759
- Publisher
- The American Society of Human Genetics
- DOI
- 10.1086/302659
- PMID
- 10577929
- PMCID
- PMC1288402
- ISSN
- 0002-9297
- eISSN
- 1537-6605
- Alternative title
- LD-Adaptive Linkage Test
- Language
- English
- Date published
- 11/23/1999
- Academic Unit
- Statistics and Actuarial Science
- Record Identifier
- 9984257633602771
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