Skip to main content
Journal cover image

Linkage disequilibrium inflates type I error rates in multipoint linkage analysis when parental genotypes are missing.

Publication ,  Journal Article
Boyles, AL; Scott, WK; Martin, ER; Schmidt, S; Li, Y-J; Ashley-Koch, A; Bass, MP; Schmidt, M; Pericak-Vance, MA; Speer, MC; Hauser, ER
Published in: Hum Hered
2005

OBJECTIVES: Describe the inflation in nonparametric multipoint LOD scores due to inter-marker linkage disequilibrium (LD) across many markers with varied allele frequencies. METHOD: Using simulated two-generation families with and without parents, we conducted nonparametric multipoint linkage analysis with 2 to 10 markers with minor allele frequencies (MAF) of 0.5 and 0.1. RESULTS: Misspecification of population haplotype frequencies by assuming linkage equilibrium caused inflated multipoint LOD scores due to inter-marker LD when parental genotypes were not included. Inflation increased as more markers in LD were included and decreased as markers in equilibrium were added. When marker allele frequencies were unequal, the r2 measure of LD was a better predictor of inflation than D'. CONCLUSION: This observation strongly supports the evaluation of LD in multipoint linkage analyses, and further suggests that unaccounted for LD may be suspected when two-point and multipoint linkage analyses show a marked disparity in regions with elevated r2 measures of LD. Given the increasing popularity of high-density genome-wide SNP screens, inter-marker LD should be a concern in future linkage studies.

Duke Scholars

Altmetric Attention Stats
Dimensions Citation Stats

Published In

Hum Hered

DOI

ISSN

0001-5652

Publication Date

2005

Volume

59

Issue

4

Start / End Page

220 / 227

Location

Switzerland

Related Subject Headings

  • Statistics, Nonparametric
  • Parents
  • Nuclear Family
  • Lod Score
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genetics & Heredity
  • Genetic Markers
  • Genetic Linkage
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Boyles, A. L., Scott, W. K., Martin, E. R., Schmidt, S., Li, Y.-J., Ashley-Koch, A., … Hauser, E. R. (2005). Linkage disequilibrium inflates type I error rates in multipoint linkage analysis when parental genotypes are missing. Hum Hered, 59(4), 220–227. https://doi.org/10.1159/000087122
Boyles, Abee L., William K. Scott, Eden R. Martin, Silke Schmidt, Yi-Ju Li, Allison Ashley-Koch, Meredyth P. Bass, et al. “Linkage disequilibrium inflates type I error rates in multipoint linkage analysis when parental genotypes are missing.Hum Hered 59, no. 4 (2005): 220–27. https://doi.org/10.1159/000087122.
Boyles AL, Scott WK, Martin ER, Schmidt S, Li Y-J, Ashley-Koch A, et al. Linkage disequilibrium inflates type I error rates in multipoint linkage analysis when parental genotypes are missing. Hum Hered. 2005;59(4):220–7.
Boyles, Abee L., et al. “Linkage disequilibrium inflates type I error rates in multipoint linkage analysis when parental genotypes are missing.Hum Hered, vol. 59, no. 4, 2005, pp. 220–27. Pubmed, doi:10.1159/000087122.
Boyles AL, Scott WK, Martin ER, Schmidt S, Li Y-J, Ashley-Koch A, Bass MP, Schmidt M, Pericak-Vance MA, Speer MC, Hauser ER. Linkage disequilibrium inflates type I error rates in multipoint linkage analysis when parental genotypes are missing. Hum Hered. 2005;59(4):220–227.
Journal cover image

Published In

Hum Hered

DOI

ISSN

0001-5652

Publication Date

2005

Volume

59

Issue

4

Start / End Page

220 / 227

Location

Switzerland

Related Subject Headings

  • Statistics, Nonparametric
  • Parents
  • Nuclear Family
  • Lod Score
  • Linkage Disequilibrium
  • Humans
  • Genotype
  • Genetics & Heredity
  • Genetic Markers
  • Genetic Linkage