An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation

Stephen J. Iturria, Jeff T. Williams, Laura Almasy, Thomas D. Dyer, John Blangero

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage. The empirical distribution of the lod scores calculated using permuted phenotypes is compared to that obtained using phenotypes simulated from the assumed underlying multivariate normal model. We make comparisons of univariate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronounced outliers. An example of a bivariate analysis is also presented.

Original languageEnglish (US)
JournalGenetic Epidemiology
Volume17
Issue numberSUPPL. 1
StatePublished - 1999
Externally publishedYes

Fingerprint

Quantitative Trait Loci
Phenotype
Lod Score

Keywords

  • Permutation test
  • Power
  • Quantitative trait locus
  • Statistical genetics

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

Iturria, S. J., Williams, J. T., Almasy, L., Dyer, T. D., & Blangero, J. (1999). An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation. Genetic Epidemiology, 17(SUPPL. 1).

An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation. / Iturria, Stephen J.; Williams, Jeff T.; Almasy, Laura; Dyer, Thomas D.; Blangero, John.

In: Genetic Epidemiology, Vol. 17, No. SUPPL. 1, 1999.

Research output: Contribution to journalArticle

Iturria, Stephen J. ; Williams, Jeff T. ; Almasy, Laura ; Dyer, Thomas D. ; Blangero, John. / An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation. In: Genetic Epidemiology. 1999 ; Vol. 17, No. SUPPL. 1.
@article{1f2bb76faf0042dca7936109369b336a,
title = "An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation",
abstract = "We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage. The empirical distribution of the lod scores calculated using permuted phenotypes is compared to that obtained using phenotypes simulated from the assumed underlying multivariate normal model. We make comparisons of univariate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronounced outliers. An example of a bivariate analysis is also presented.",
keywords = "Permutation test, Power, Quantitative trait locus, Statistical genetics",
author = "Iturria, {Stephen J.} and Williams, {Jeff T.} and Laura Almasy and Dyer, {Thomas D.} and John Blangero",
year = "1999",
language = "English (US)",
volume = "17",
journal = "Genetic Epidemiology",
issn = "0741-0395",
publisher = "Wiley-Liss Inc.",
number = "SUPPL. 1",

}

TY - JOUR

T1 - An empirical test of the significance of an observed quantitative trait locus effect that preserves additive genetic variation

AU - Iturria, Stephen J.

AU - Williams, Jeff T.

AU - Almasy, Laura

AU - Dyer, Thomas D.

AU - Blangero, John

PY - 1999

Y1 - 1999

N2 - We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage. The empirical distribution of the lod scores calculated using permuted phenotypes is compared to that obtained using phenotypes simulated from the assumed underlying multivariate normal model. We make comparisons of univariate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronounced outliers. An example of a bivariate analysis is also presented.

AB - We propose a constrained permutation test that assesses the significance of an observed quantitative trait locus effect against a background of genetic and environmental variation. Permutations of phenotypes are not selected at random, but rather are chosen in a manner that attempts to maintain the additive genetic variability in phenotypes. Such a constraint maintains the nonindependence among observations under the null hypothesis of no linkage. The empirical distribution of the lod scores calculated using permuted phenotypes is compared to that obtained using phenotypes simulated from the assumed underlying multivariate normal model. We make comparisons of univariate analyses for both a quantitative phenotype that appears consistent with a multivariate normal model and a quantitative phenotype containing pronounced outliers. An example of a bivariate analysis is also presented.

KW - Permutation test

KW - Power

KW - Quantitative trait locus

KW - Statistical genetics

UR - http://www.scopus.com/inward/record.url?scp=0032758862&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0032758862&partnerID=8YFLogxK

M3 - Article

C2 - 10597431

AN - SCOPUS:0032758862

VL - 17

JO - Genetic Epidemiology

JF - Genetic Epidemiology

SN - 0741-0395

IS - SUPPL. 1

ER -