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Comparative assessment of methods for estimating individual genome-wide homozygosity-by-descent from human genomic data

Ozren Polašek12*, Caroline Hayward3, Celine Bellenguez45, Veronique Vitart3, Ivana Kolčić2, Ruth McQuillan1, Vanja Saftić6, Ulf Gyllensten7, James F Wilson1, Igor Rudan189, Alan F Wright3, Harry Campbell1 and Anne-Louise Leutenegger45

Author Affiliations

1 Public Health Sciences, University of Edinburgh, Edinburgh, UK

2 Department of Medical Statistics, Epidemiology and Medical Informatics, Andrija Stampar School of Public Health, Medical School, University of Zagreb, Zagreb, Croatia

3 Human Genetics Unit, Medical Research Council, Edinburgh, UK

4 Inserm, U535, Villejuif, France

5 University Paris-Sud, IFR69, UMR_S535, Villejuif, France

6 University Hospital Sestre Milosrdnice, Zagreb, Croatia

7 Department of Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden

8 Gen-info d.o.o., Zagreb, Croatia

9 Croatian Centre for Global Health, University of Split, Split, Croatia

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BMC Genomics 2010, 11:139  doi:10.1186/1471-2164-11-139

Published: 25 February 2010



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.


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.


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.