Detection of sharing by descent, long-range phasing and haplotype imputation

By A. Kong, G. Másson, M. Frigge, A. Gylfason, Pasha Zusmanovich, G. Thorleifsson, Pall I. Olason, A. Ingason, S. Steinberg, T. Rafnar and 7 more. Nature Genetics, 2008

486 citations recorded by the source corpus.

Uncertainty about the phase of strings of SNPs creates complications in genetic analysis, although methods have been developed for phasing population-based samples. However, these methods can only phase a small number of SNPs effectively and become unreliable when applied to SNPs spanning many linkage disequilibrium (LD) blocks. Here we show how to phase more than 1,000 SNPs simultaneously for a large fraction of the 35,528 Icelanders genotyped by Illumina chips. Moreover, haplotypes that are identical by descent (IBD) between close and distant relatives, for example, those separated by ten meioses or more, can often be reliably detected. This method is particularly powerful in studies of the inheritance of recurrent mutations and fine-scale recombinations in large sample sets. A further extension of the method allows us to impute long haplotypes for individuals who are not genotyped.

Subfields: Genetics

View Paper: https://www.semanticscholar.org/paper/90c22400b0bd559d2b4c0e359190134c791338e2

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Citations in the corpus

A Flexible and Accurate Genotype Imputation Method for the Next Generation of Genome-Wide Association Studies (2009, methodology): “One way of understanding our approach is by comparison to the phasing method of Kong et al. [19].”
A new approach for efficient genotype imputation using information from relatives (2014, methodology): “Even when pedigree information is not available, family information can be captured by searching for long haplotypes [11].”
Fast and accurate long-range phasing in a UK Biobank cohort (2015, unknown): “Second, LRP by itself can phase only sites at which the proband has at least one homozygous relative; for cohorts representing a sizable fraction of a population, only 5% of sites may be left unphased [13], but for smaller cohorts, this fraction may exceed 25% even in isolated populations [28], limi”
Fast two-stage phasing of large-scale sequence data. (2021, methodology): “The fast-PHASE, 17 Beagle, 18 long-range phasing, 19 and Mach 20 methods were among the ﬁrst methods designed for genome-wide data.”
A fast, powerful method for detecting identity by descent. (2011, methodology): “The fastIBD method will also be useful in other applications, such as population-based linkage in founder populations(26) and improving haplotype phase inference and imputation.(14)”
Whole population, genome-wide mapping of hidden relatedness. (2009, methodology): “Recently, IBD has been reported in Icelanders (Kong et al. 2008) based on statistic arguments and pairwise analysis of samples.”
Missing heritability and strategies for finding the underlying causes of complex disease (2010, background): “Phase-dependent interactions between variants that are not in linkage disequilibrium and that are difficult to detect without long-range haplotype”
Fast and accurate genotype imputation in genome-wide association studies through pre-phasing (2012, background): “In founder populations 14 , long-range haplotypes can be estimated very accurately, even with modest sample sizes 9 .”