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On computation of p-values in parametric linkage analysis

Kurbasic, Azra LU and Hossjer, O (2004) In Human Heredity 57(4). p.207-219
Abstract
Parametric linkage analysis is usually used to find chromosomal regions linked to a disease (phenotype) that is described with a specific genetic model. This is done by investigating the relations between the disease and genetic markers, that is, well-characterized loci of known position with a clear Mendelian mode of inheritance. Assume we have found an interesting region on a chromosome that we suspect is linked to the disease. Then we want to test the hypothesis of no linkage versus the alternative one of linkage. As a measure we use the maximal lod score Z(max). It is well known that the maximal lod score has asymptotically a (2 ln 10)(-1) x (1/2 chi(2)(0) + 1/2 chi(2)(1)) distribution under the null hypothesis of no linkage when only... (More)
Parametric linkage analysis is usually used to find chromosomal regions linked to a disease (phenotype) that is described with a specific genetic model. This is done by investigating the relations between the disease and genetic markers, that is, well-characterized loci of known position with a clear Mendelian mode of inheritance. Assume we have found an interesting region on a chromosome that we suspect is linked to the disease. Then we want to test the hypothesis of no linkage versus the alternative one of linkage. As a measure we use the maximal lod score Z(max). It is well known that the maximal lod score has asymptotically a (2 ln 10)(-1) x (1/2 chi(2)(0) + 1/2 chi(2)(1)) distribution under the null hypothesis of no linkage when only one point ( one marker) on the chromosome is studied. In this paper, we show, both by simulations and theoretical arguments, that the null hypothesis distribution of Z(max) has no simple form when more than one marker is used ( multipoint analysis). In fact, the distribution of Z(max) depends on the number of families, their structure, the assumed genetic model, marker denseness, and marker informativity. This means that a constant critical limit of Z(max) leads to tests associated with different significance levels. Because of the above-mentioned problems, from the statistical point of view the maximal lod score should be supplemented by a p-value when results are reported. Copyright (C) 2004 S. Karger AG, Basel. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
pointwise/genomewide p-value, linkage analysis, lod score distribution
in
Human Heredity
volume
57
issue
4
pages
207 - 219
publisher
Karger
external identifiers
  • wos:000226013000006
  • pmid:15583427
  • scopus:10844237959
ISSN
1423-0062
DOI
10.1159/000081448
language
English
LU publication?
yes
id
00ac8464-50ab-498f-b3d6-33a3a6260f44 (old id 257974)
date added to LUP
2007-10-23 19:57:28
date last changed
2017-01-01 04:43:50
@article{00ac8464-50ab-498f-b3d6-33a3a6260f44,
  abstract     = {Parametric linkage analysis is usually used to find chromosomal regions linked to a disease (phenotype) that is described with a specific genetic model. This is done by investigating the relations between the disease and genetic markers, that is, well-characterized loci of known position with a clear Mendelian mode of inheritance. Assume we have found an interesting region on a chromosome that we suspect is linked to the disease. Then we want to test the hypothesis of no linkage versus the alternative one of linkage. As a measure we use the maximal lod score Z(max). It is well known that the maximal lod score has asymptotically a (2 ln 10)(-1) x (1/2 chi(2)(0) + 1/2 chi(2)(1)) distribution under the null hypothesis of no linkage when only one point ( one marker) on the chromosome is studied. In this paper, we show, both by simulations and theoretical arguments, that the null hypothesis distribution of Z(max) has no simple form when more than one marker is used ( multipoint analysis). In fact, the distribution of Z(max) depends on the number of families, their structure, the assumed genetic model, marker denseness, and marker informativity. This means that a constant critical limit of Z(max) leads to tests associated with different significance levels. Because of the above-mentioned problems, from the statistical point of view the maximal lod score should be supplemented by a p-value when results are reported. Copyright (C) 2004 S. Karger AG, Basel.},
  author       = {Kurbasic, Azra and Hossjer, O},
  issn         = {1423-0062},
  keyword      = {pointwise/genomewide p-value,linkage analysis,lod score distribution},
  language     = {eng},
  number       = {4},
  pages        = {207--219},
  publisher    = {Karger},
  series       = {Human Heredity},
  title        = {On computation of p-values in parametric linkage analysis},
  url          = {http://dx.doi.org/10.1159/000081448},
  volume       = {57},
  year         = {2004},
}