title: Comparative assessment of methods for estimating individual genome-wide homozygosity-by-descent from human genomic data.
abstract: BACKGROUND
  Genome-wide homozygosity estimation from genomic data is becoming an increasingly interesting research topic. The aim of this study was to compare different methods for estimating individual homozygosity-by-descent based on the information from human genome-wide scans rather than genealogies. We considered the four most commonly used methods and investigated their applicability to single-nucleotide polymorphism (SNP) data in both a simulation study and by using the human genotyped data. A total of 986 inhabitants from the isolated Island of Vis, Croatia (where inbreeding is present, but no pedigree-based inbreeding was observed at the level of F > 0.0625) were included in this study. All individuals were genotyped with the Illumina HumanHap300 array with 317,503 SNP markers.
  
  
  RESULTS
  Simulation data suggested that multi-point FEstim is the method most strongly correlated to true homozygosity-by-descent. Correlation coefficients between the homozygosity-by-descent estimates were high but only for inbred individuals, with nearly absolute correlation between single-point measures.
  
  
  CONCLUSIONS
  Deciding who is really inbred is a methodological challenge where multi-point approaches can be very helpful once the set of SNP markers is filtered to remove linkage disequilibrium. The use of several different methodological approaches and hence different homozygosity measures can help to distinguish between homozygosity-by-state and homozygosity-by-descent in studies investigating the effects of genomic autozygosity on human health.
authors.affiliation: Public Health Sciences, University of Edinburgh, Edinburgh, UK. opolasek@gmail.com
authors.forename: Ozren
authors.initials: O
authors.lastname: Polasek
authors.forename: Caroline
authors.initials: C
authors.lastname: Hayward
authors.forename: Celine
authors.initials: C
authors.lastname: Bellenguez
authors.forename: Veronique
authors.initials: V
authors.lastname: Vitart
authors.forename: Ivana
authors.initials: I
authors.lastname: Kolcić
authors.forename: Ruth
authors.initials: R
authors.lastname: McQuillan
authors.forename: Vanja
authors.initials: V
authors.lastname: Saftić
authors.forename: Ulf
authors.initials: U
authors.lastname: Gyllensten
authors.forename: James F
authors.initials: JF
authors.lastname: Wilson
authors.forename: Igor
authors.initials: I
authors.lastname: Rudan
authors.forename: Alan F
authors.initials: AF
authors.lastname: Wright
authors.forename: Harry
authors.initials: H
authors.lastname: Campbell
authors.forename: Anne-Louise
authors.initials: AL
authors.lastname: Leutenegger
mesh_terms: D003198:Computer Simulation; D003241:Consanguinity; D017523:Croatia; D056726:Genetic Association Studies / Q000379:methods*; D015894:Genome, Human; D005838:Genotype; D006720:Homozygote; D006801:Humans; D040582:Inheritance Patterns; D016013:Likelihood Functions; D020641:Polymorphism, Single Nucleotide