A test for linkage and association in general pedigrees

The pedigree disequilibrium test

Eden R Martin, Stephanie A. Monks, Liling L. Warren, Norman L. Kaplan

Research output: Contribution to journalArticle

512 Citations (Scopus)

Abstract

Family-based tests of linkage disequilibrium typically are based on nuclear-family data including affected individuals and their parents or their unaffected siblings. A limitation of such tests is that they generally are not valid tests of association when data from related nuclear families from larger pedigrees are used. Standard methods require selection of a single nuclear family from any extended pedigrees when testing for linkage disequilibrium. Often data are available for larger pedigrees, and it would be desirable to have a valid test of linkage disequilibrium that can use all potentially informative data. In this study, we present the pedigree disequilibrium test (PDT) for analysis of linkage disequilibrium in general pedigrees. The PDT can use data from related nuclear families from extended pedigrees and is valid even when there is population substructure. Using computer simulations, we demonstrated validity of the test when the asymptotic distribution is used to assess the significance, and examined statistical power. Power simulations demonstrate that, when extended pedigree data are available, substantial gains in power can be attained by use of the PDT rather than existing methods that use only a subset of the data. Furthermore, the PDT remains more powerful even when there is misclassification of unaffected individuals. Our simulations suggest that there may be advantages to using the PDT even if the data consist of independent families without extended family information. Thus, the PDT provides a general test of linkage disequilibrium that can be widely applied to different data structures.

Original languageEnglish
Pages (from-to)146-154
Number of pages9
JournalAmerican Journal of Human Genetics
Volume67
Issue number1
DOIs
StatePublished - Aug 5 2000
Externally publishedYes

Fingerprint

Pedigree
Linkage Disequilibrium
Nuclear Family
Computer Simulation
Siblings
Parents

ASJC Scopus subject areas

  • Genetics

Cite this

A test for linkage and association in general pedigrees : The pedigree disequilibrium test. / Martin, Eden R; Monks, Stephanie A.; Warren, Liling L.; Kaplan, Norman L.

In: American Journal of Human Genetics, Vol. 67, No. 1, 05.08.2000, p. 146-154.

Research output: Contribution to journalArticle

Martin, Eden R ; Monks, Stephanie A. ; Warren, Liling L. ; Kaplan, Norman L. / A test for linkage and association in general pedigrees : The pedigree disequilibrium test. In: American Journal of Human Genetics. 2000 ; Vol. 67, No. 1. pp. 146-154.
@article{cff225100ab4417487c159133038d255,
title = "A test for linkage and association in general pedigrees: The pedigree disequilibrium test",
abstract = "Family-based tests of linkage disequilibrium typically are based on nuclear-family data including affected individuals and their parents or their unaffected siblings. A limitation of such tests is that they generally are not valid tests of association when data from related nuclear families from larger pedigrees are used. Standard methods require selection of a single nuclear family from any extended pedigrees when testing for linkage disequilibrium. Often data are available for larger pedigrees, and it would be desirable to have a valid test of linkage disequilibrium that can use all potentially informative data. In this study, we present the pedigree disequilibrium test (PDT) for analysis of linkage disequilibrium in general pedigrees. The PDT can use data from related nuclear families from extended pedigrees and is valid even when there is population substructure. Using computer simulations, we demonstrated validity of the test when the asymptotic distribution is used to assess the significance, and examined statistical power. Power simulations demonstrate that, when extended pedigree data are available, substantial gains in power can be attained by use of the PDT rather than existing methods that use only a subset of the data. Furthermore, the PDT remains more powerful even when there is misclassification of unaffected individuals. Our simulations suggest that there may be advantages to using the PDT even if the data consist of independent families without extended family information. Thus, the PDT provides a general test of linkage disequilibrium that can be widely applied to different data structures.",
author = "Martin, {Eden R} and Monks, {Stephanie A.} and Warren, {Liling L.} and Kaplan, {Norman L.}",
year = "2000",
month = "8",
day = "5",
doi = "10.1086/302957",
language = "English",
volume = "67",
pages = "146--154",
journal = "American Journal of Human Genetics",
issn = "0002-9297",
publisher = "Cell Press",
number = "1",

}

TY - JOUR

T1 - A test for linkage and association in general pedigrees

T2 - The pedigree disequilibrium test

AU - Martin, Eden R

AU - Monks, Stephanie A.

AU - Warren, Liling L.

AU - Kaplan, Norman L.

PY - 2000/8/5

Y1 - 2000/8/5

N2 - Family-based tests of linkage disequilibrium typically are based on nuclear-family data including affected individuals and their parents or their unaffected siblings. A limitation of such tests is that they generally are not valid tests of association when data from related nuclear families from larger pedigrees are used. Standard methods require selection of a single nuclear family from any extended pedigrees when testing for linkage disequilibrium. Often data are available for larger pedigrees, and it would be desirable to have a valid test of linkage disequilibrium that can use all potentially informative data. In this study, we present the pedigree disequilibrium test (PDT) for analysis of linkage disequilibrium in general pedigrees. The PDT can use data from related nuclear families from extended pedigrees and is valid even when there is population substructure. Using computer simulations, we demonstrated validity of the test when the asymptotic distribution is used to assess the significance, and examined statistical power. Power simulations demonstrate that, when extended pedigree data are available, substantial gains in power can be attained by use of the PDT rather than existing methods that use only a subset of the data. Furthermore, the PDT remains more powerful even when there is misclassification of unaffected individuals. Our simulations suggest that there may be advantages to using the PDT even if the data consist of independent families without extended family information. Thus, the PDT provides a general test of linkage disequilibrium that can be widely applied to different data structures.

AB - Family-based tests of linkage disequilibrium typically are based on nuclear-family data including affected individuals and their parents or their unaffected siblings. A limitation of such tests is that they generally are not valid tests of association when data from related nuclear families from larger pedigrees are used. Standard methods require selection of a single nuclear family from any extended pedigrees when testing for linkage disequilibrium. Often data are available for larger pedigrees, and it would be desirable to have a valid test of linkage disequilibrium that can use all potentially informative data. In this study, we present the pedigree disequilibrium test (PDT) for analysis of linkage disequilibrium in general pedigrees. The PDT can use data from related nuclear families from extended pedigrees and is valid even when there is population substructure. Using computer simulations, we demonstrated validity of the test when the asymptotic distribution is used to assess the significance, and examined statistical power. Power simulations demonstrate that, when extended pedigree data are available, substantial gains in power can be attained by use of the PDT rather than existing methods that use only a subset of the data. Furthermore, the PDT remains more powerful even when there is misclassification of unaffected individuals. Our simulations suggest that there may be advantages to using the PDT even if the data consist of independent families without extended family information. Thus, the PDT provides a general test of linkage disequilibrium that can be widely applied to different data structures.

UR - http://www.scopus.com/inward/record.url?scp=0033910787&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0033910787&partnerID=8YFLogxK

U2 - 10.1086/302957

DO - 10.1086/302957

M3 - Article

VL - 67

SP - 146

EP - 154

JO - American Journal of Human Genetics

JF - American Journal of Human Genetics

SN - 0002-9297

IS - 1

ER -