On computation of pvalues in parametric linkage analysis
(2004) In Human Heredity 57(4). p.207219 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, wellcharacterized 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, wellcharacterized 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 abovementioned problems, from the statistical point of view the maximal lod score should be supplemented by a pvalue when results are reported. Copyright (C) 2004 S. Karger AG, Basel. (Less)
Please use this url to cite or link to this publication:
http://lup.lub.lu.se/record/257974
 author
 Kurbasic, Azra ^{LU} and Hossjer, O
 organization
 publishing date
 2004
 type
 Contribution to journal
 publication status
 published
 subject
 keywords
 pointwise/genomewide pvalue, 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
 14230062
 DOI
 10.1159/000081448
 language
 English
 LU publication?
 yes
 id
 00ac846450ab498fb3d633a3a6260f44 (old id 257974)
 date added to LUP
 20071023 19:57:28
 date last changed
 20170101 04:43:50
@article{00ac846450ab498fb3d633a3a6260f44, 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, wellcharacterized 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 abovementioned problems, from the statistical point of view the maximal lod score should be supplemented by a pvalue when results are reported. Copyright (C) 2004 S. Karger AG, Basel.}, author = {Kurbasic, Azra and Hossjer, O}, issn = {14230062}, keyword = {pointwise/genomewide pvalue,linkage analysis,lod score distribution}, language = {eng}, number = {4}, pages = {207219}, publisher = {Karger}, series = {Human Heredity}, title = {On computation of pvalues in parametric linkage analysis}, url = {http://dx.doi.org/10.1159/000081448}, volume = {57}, year = {2004}, }