Examining the effect of linkage disequilibrium on multipoint linkage analysis.
Most linkage programs assume linkage equilibrium among multiple linked markers. This assumption may lead to bias for tightly linked markers where strong linkage disequilibrium (LD) exists. We used simulated data from Genetic Analysis Workshop 14 to examine the possible effect of LD on multipoint linkage analysis. Single-nucleotide polymorphism packets from a non-disease-related region that was generated with LD were used for both model-free and parametric linkage analyses. Results showed that high LD among markers can induce false-positive evidence of linkage for affected sib-pair analysis when parental data are missing. Bias can be eliminated with parental data and can be reduced when additional markers not in LD are included in the analyses.
Huang
Qiqing
Q
Department of Epidemiology, University of Texas M. D. Anderson Cancer Center, Houston, Texas, USA. qhuang@prdus.jnj.com
Shete
Sanjay
S
Swartz
Michael
M
Amos
Christopher I
CI
D005819:Genetic Markers; D005828:Genetics, Population; D006801:Humans; D015810:Linkage Disequilibrium / Q000235:genetics*; D008126:Lod Score; D008957:Models, Genetic; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D015203:Reproducibility of Results
D005819:Genetic Markers