Power of quantitative trait locus mapping for polygenic binary traits using generalized and regression interval mapping in multi-family half-sib designs.
A generalized interval mapping (GIM) method to map quantitative trait loci (QTL) for binary polygenic traits in a multi-family half-sib design is developed based on threshold theory and implemented using a Newton-Raphson algorithm. Statistical power and bias of QTL mapping for binary traits by GIM is compared with linear regression interval mapping (RIM) using simulation. Data on 20 paternal half-sib families were simulated with two genetic markers that bracketed an additive QTL. Data simulated and analysed were: (1) data on the underlying normally distributed liability (NDL) scale, (2) binary data created by truncating NDL data based on three thresholds yielding data sets with three different incidences, and (3) NDL data with polygenic and QTL effects reduced by a proportion equal to the ratio of the heritabilities on the binary versus NDL scale (reduced-NDL). Binary data were simulated with and without systematic environmental (herd) effects in an unbalanced design. GIM and RIM gave similar power to detect the QTL and similar estimates of QTL location, effects and variances. Presence of fixed effects caused differences in bias between RIM and GIM, where GIM showed smaller bias which was affected less by incidence. The original NDL data had higher power and lower bias in QTL parameter estimates than binary and reduced-NDL data. RIM for reduced-NDL and binary data gave similar power and estimates of QTL parameters, indicating that the impact of the binary nature of data on QTL analysis is equivalent to its impact on heritability.
Kadarmideen
H N
HN
Department of Animal and Poultry Science, University of Guelph, Guelph, ON N1G 2W1, Canada. h.kadarmideen@ed.sac.ac.uk
Janss
L L
LL
Dekkers
J C
JC
D000465:Algorithms; D000483:Alleles; D000818:Animals; D002874:Chromosome Mapping / Q000379:methods*; D003198:Computer Simulation / Q000706:statistics & numerical data; D005190:Family; D008040:Genetic Linkage; D014644:Genetic Variation; D005838:Genotype; D006801:Humans; D016013:Likelihood Functions; D018895:Microsatellite Repeats; D008957:Models, Genetic; D020412:Multifactorial Inheritance / Q000235:genetics*; D010641:Phenotype; D019655:Quantitative Trait, Heritable; D011995:Recombination, Genetic; D012044:Regression Analysis