title: Using selection index theory to estimate consistency of multi-locus linkage disequilibrium across populations.
abstract: BACKGROUND
  The potential of combining multiple populations in genomic prediction is depending on the consistency of linkage disequilibrium (LD) between SNPs and QTL across populations. We investigated consistency of multi-locus LD across populations using selection index theory and investigated the relationship between consistency of multi-locus LD and accuracy of genomic prediction across different simulated scenarios. In the selection index, QTL genotypes were considered as breeding goal traits and SNP genotypes as index traits, based on LD among SNPs and between SNPs and QTL. The consistency of multi-locus LD across populations was computed as the accuracy of predicting QTL genotypes in selection candidates using a selection index derived in the reference population. Different scenarios of within and across population genomic prediction were evaluated, using all SNPs or only the four neighboring SNPs of a simulated QTL. Phenotypes were simulated using different numbers of QTL underlying the trait. The relationship between the calculated consistency of multi-locus LD and accuracy of genomic prediction using a GBLUP type of model was investigated.
  
  
  RESULTS
  The accuracy of predicting QTL genotypes, i.e. the measure describing consistency of multi-locus LD, was much lower for across population scenarios compared to within population scenarios, and was lower when QTL had a low MAF compared to QTL randomly selected from the SNPs. Consistency of multi-locus LD was highly correlated with the realized accuracy of genomic prediction across different scenarios and the correlation was higher when QTL were weighted according to their effects in the selection index instead of weighting QTL equally. By only considering neighboring SNPs of QTL, accuracy of predicting QTL genotypes within population decreased, but it substantially increased the accuracy across populations.
  
  
  CONCLUSIONS
  Consistency of multi-locus LD across populations is a characteristic of the properties of the QTL in the investigated populations and can provide more insight in underlying reasons for a low empirical accuracy of across population genomic prediction. By focusing in genomic prediction models only on neighboring SNPs of QTL, multi-locus LD is more consistent across populations since only short-range LD is considered, and accuracy of predicting QTL genotypes of individuals from another population is increased.
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, 6700 AH, Wageningen, The Netherlands. yvonne.wientjes@wur.nl.|Animal Breeding and Genomics Centre, Wageningen University, 6700 AH, Wageningen, The Netherlands. yvonne.wientjes@wur.nl.
authors.forename: Yvonne C J
authors.initials: YC
authors.lastname: Wientjes
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, 6700 AH, Wageningen, The Netherlands. roel.veerkamp@wur.nl.|Animal Breeding and Genomics Centre, Wageningen University, 6700 AH, Wageningen, The Netherlands. roel.veerkamp@wur.nl.
authors.forename: Roel F
authors.initials: RF
authors.lastname: Veerkamp
authors.affiliation: Animal Breeding and Genomics Centre, Wageningen UR Livestock Research, 6700 AH, Wageningen, The Netherlands. mario.calus@wur.nl.
authors.forename: Mario P L
authors.initials: MP
authors.lastname: Calus
mesh_terms: D000465:Algorithms; D001947:Breeding; D003198:Computer Simulation; D008040:Genetic Linkage; D056426:Genetic Loci; D005828:Genetics, Population; D023281:Genomics / Q000379:methods; D005838:Genotype; D015810:Linkage Disequilibrium; D008957:Models, Genetic; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D040641:Quantitative Trait Loci; D015203:Reproducibility of Results; D012641:Selection, Genetic