IBDkin: fast estimation of kinship coefficients from identity by descent segments.
Ontology highlight
ABSTRACT: Motivation
Estimation of pairwise kinship coefficients in large datasets is computationally challenging because the number of related individuals increases quadratically with sample size.Results
We present IBDkin, a software package written in C for estimating kinship coefficients from identity by descent (IBD) segments. We use IBDkin to estimate kinship coefficients for 7.95 billion pairs of individuals in the UK Biobank who share at least one detected IBD segment with length ≥ 4 cM.Availability and implementation
https://github.com/YingZhou001/IBDkin.Supplementary information
Supplementary data are available at Bioinformatics online.
SUBMITTER: Zhou Y
PROVIDER: S-EPMC7750976 | biostudies-literature |
REPOSITORIES: biostudies-literature
Similar Datasets
Project description:MotivationEstimating the individual inbreeding coefficient and pairwise kinship is an important problem in human genetics (e.g. in disease mapping) and in animal and plant genetics (e.g. inbreeding design). Existing methods, such as sample correlation-based genetic relationship matrix, KING, and UKin, are either biased, or not able to estimate inbreeding coefficients, or produce a large proportion of negative estimates that are difficult to interpret. This limitation of existing methods is partly due to failure to explicitly model inbreeding. Since all humans are inbred to various degrees by virtue of shared ancestries, it is prudent to account for inbreeding when inferring kinship between individuals.ResultsWe present "Kindred," an approach that estimates inbreeding and kinship by modeling latent identity-by-descent states that accounts for all possible allele sharing-including inbreeding-between two individuals. Kindred used non-negative least squares method to fit the model, which not only increases computation efficiency compared to the maximum likelihood method, but also guarantees non-negativity of the kinship estimates. Through simulation, we demonstrate the high accuracy and non-negativity of kinship estimates by Kindred. By selecting a subset of SNPs that are similar in allele frequencies across different continental populations, Kindred can accurately estimate kinship between admixed samples. In addition, we demonstrate that the realized kinship matrix estimated by Kindred is effective in reducing genomic control values via linear mixed model in genome-wide association studies. Finally, we demonstrate that Kindred produces sensible heritability estimates on an Australian height dataset.Availability and implementationKindred is implemented in C with multi-threading. It takes vcf file or stream as input and works seamlessly with bcftools. Kindred is freely available at https://github.com/haplotype/kindred.
| S-EPMC10902678 | biostudies-literature
Project description:Existing methods for estimating historical effective population size from genetic data have been unable to accurately estimate effective population size during the most recent past. We present a non-parametric method for accurately estimating recent effective population size by using inferred long segments of identity by descent (IBD). We found that inferred segments of IBD contain information about effective population size from around 4 generations to around 50 generations ago for SNP array data and to over 200 generations ago for sequence data. In human populations that we examined, the estimates of effective size were approximately one-third of the census size. We estimate the effective population size of European-ancestry individuals in the UK four generations ago to be eight million and the effective population size of Finland four generations ago to be 0.7 million. Our method is implemented in the open-source IBDNe software package.
| S-EPMC4564943 | biostudies-literature
Project description:Segments of identity by descent (IBD) are used in many genetic analyses. We present a method for detecting identical-by-descent haplotype segments in phased genotype data. Our method, called hap-IBD, combines a compressed representation of haplotype data, the positional Burrows-Wheeler transform, and multi-threaded execution to produce very fast analysis times. An attractive feature of hap-IBD is its simplicity: the input parameters clearly and precisely define the IBD segments that are reported, so that program correctness can be confirmed by users. We evaluate hap-IBD and four state-of-the-art IBD segment detection methods (GERMLINE, iLASH, RaPID, and TRUFFLE) using UK Biobank chromosome 20 data and simulated sequence data. We show that hap-IBD detects IBD segments faster and more accurately than competing methods, and that hap-IBD is the only method that can rapidly and accurately detect short 2-4 centiMorgan (cM) IBD segments in the full UK Biobank data. Analysis of 485,346 UK Biobank samples through the use of hap-IBD with 12 computational threads detects 231.5 billion autosomal IBD segments with length ≥2 cM in 24.4 h.
| S-EPMC7118582 | biostudies-literature
Project description:Recombination rates vary significantly across the genome, and estimates of recombination rates are needed for downstream analyses such as haplotype phasing and genotype imputation. Existing methods for recombination rate estimation are limited by insufficient amounts of informative genetic data or by high computational cost. We present a method and software, called IBDrecomb, for using segments of identity by descent to infer recombination rates. IBDrecomb can be applied to sequenced population cohorts to obtain high-resolution, population-specific recombination maps. In simulated admixed data, IBDrecomb obtains higher accuracy than admixture-based estimation of recombination rates. When applied to 2,500 simulated individuals, IBDrecomb obtains similar accuracy to a linkage-disequilibrium (LD)-based method applied to 96 individuals (the largest number for which computation is tractable). Compared to LD-based maps, our IBD-based maps have the advantage of estimating recombination rates in the recent past rather than the distant past. We used IBDrecomb to generate new recombination maps for European Americans and for African Americans from TOPMed sequence data from the Framingham Heart Study (1,626 unrelated individuals) and the Jackson Heart Study (2,046 unrelated individuals), and we compare them to LD-based, admixture-based, and family-based maps.
| S-EPMC7332656 | biostudies-literature
Project description:Long DNA segments shared between two individuals, known as identity-by-descent (IBD), reveal recent genealogical connections. Here we introduce ancIBD, a method for identifying IBD segments in ancient human DNA (aDNA) using a hidden Markov model and imputed genotype probabilities. We demonstrate that ancIBD accurately identifies IBD segments >8 cM for aDNA data with an average depth of >0.25× for whole-genome sequencing or >1× for 1240k single nucleotide polymorphism capture data. Applying ancIBD to 4,248 ancient Eurasian individuals, we identify relatives up to the sixth degree and genealogical connections between archaeological groups. Notably, we reveal long IBD sharing between Corded Ware and Yamnaya groups, indicating that the Yamnaya herders of the Pontic-Caspian Steppe and the Steppe-related ancestry in various European Corded Ware groups share substantial co-ancestry within only a few hundred years. These results show that detecting IBD segments can generate powerful insights into the growing aDNA record, both on a small scale relevant to life stories and on a large scale relevant to major cultural-historical events.
| S-EPMC10786714 | biostudies-literature
Project description:Inference of individual ancestry coefficients, which is important for population genetic and association studies, is commonly performed using computer-intensive likelihood algorithms. With the availability of large population genomic data sets, fast versions of likelihood algorithms have attracted considerable attention. Reducing the computational burden of estimation algorithms remains, however, a major challenge. Here, we present a fast and efficient method for estimating individual ancestry coefficients based on sparse nonnegative matrix factorization algorithms. We implemented our method in the computer program sNMF and applied it to human and plant data sets. The performances of sNMF were then compared to the likelihood algorithm implemented in the computer program ADMIXTURE. Without loss of accuracy, sNMF computed estimates of ancestry coefficients with runtimes ?10-30 times shorter than those of ADMIXTURE.
| S-EPMC3982712 | biostudies-literature
Project description:We present a method, fastIBD, for finding tracts of identity by descent (IBD) between pairs of individuals. FastIBD can be applied to thousands of samples across genome-wide SNP data and is significantly more powerful for finding short tracts of IBD than existing methods for finding IBD tracts in such data. We show that fastIBD can detect facets of population structure that are not revealed by other methods. In the Wellcome Trust Case Control Consortium bipolar disorder case-control data, we find a genome-wide excess of IBD in case-case pairs of individuals compared to control-control pairs. We show that this excess can be explained by the geographical clustering of cases. We also show that it is possible to use fastIBD to generate highly accurate estimates of genome-wide IBD sharing between pairs of distant relatives. This is useful for estimation of relationship and for adjusting for relatedness in association studies. FastIBD is incorporated in the freely available Beagle software package.
| S-EPMC3035716 | biostudies-literature
Project description:Identity-by-descent (IBD) is a fundamental concept in genetics with many applications. In a common definition, two haplotypes are said to share an IBD segment if that segment is inherited from a recent shared common ancestor without intervening recombination. Segments several cM long can be efficiently detected by a number of algorithms using high-density SNP array data from a population sample, and there are currently efforts to detect shorter segments from sequencing. Here, we study a problem of identifiability: because existing approaches detect IBD based on contiguous segments of identity-by-state, inferred long segments of IBD may arise from the conflation of smaller, nearby IBD segments. We quantified this effect using coalescent simulations, finding that significant proportions of inferred segments 1-2 cM long are results of conflations of two or more shorter segments, each at least 0.2 cM or longer, under demographic scenarios typical for modern humans for all programs tested. The impact of such conflation is much smaller for longer (> 2 cM) segments. This biases the inferred IBD segment length distribution, and so can affect downstream inferences that depend on the assumption that each segment of IBD derives from a single common ancestor. As an example, we present and analyze an estimator of the de novo mutation rate using IBD segments, and demonstrate that unmodeled conflation leads to underestimates of the ages of the common ancestors on these segments, and hence a significant overestimate of the mutation rate. Understanding the conflation effect in detail will make its correction in future methods more tractable.
| S-EPMC4856080 | biostudies-literature
Project description:We present a novel method, IBDLD, for estimating the probability of identity by descent (IBD) for a pair of related individuals at a locus, given dense genotype data and a pedigree of arbitrary size and complexity. IBDLD overcomes the challenges of exact multipoint estimation of IBD in pedigrees of potentially large size and eliminates the difficulty of accommodating the background linkage disequilibrium (LD) that is present in high-density genotype data. We show that IBDLD is much more accurate at estimating the true IBD sharing than methods that remove LD by pruning SNPs and is highly robust to pedigree errors or other forms of misspecified relationships. The method is fast and can be used to estimate the probability for each possible IBD sharing state at every SNP from a high-density genotyping array for hundreds of thousands of pairs of individuals. We use it to estimate point-wise and genomewide IBD sharing between 185,745 pairs of subjects all of whom are related through a single, large and complex 13-generation pedigree and genotyped with the Affymetrix 500 k chip. We find that we are able to identify the true pedigree relationship for individuals who were misidentified in the collected data and estimate empirical kinship coefficients that can be used in follow-up QTL mapping studies. IBDLD is implemented as an open source software package and is freely available.
| S-EPMC3587128 | biostudies-literature
Project description:Identity-by-descent (IBD) inference is the problem of establishing a genetic connection between two individuals through a genomic segment that is inherited by both individuals from a recent common ancestor. IBD inference is an important preceding step in a variety of population genomic studies, ranging from demographic studies to linking genomic variation with phenotype and disease. The problem of accurate IBD detection has become increasingly challenging with the availability of large collections of human genotypes and genomes: Given a cohort's size, a quadratic number of pairwise genome comparisons must be performed. Therefore, computation time and the false discovery rate can also scale quadratically. To enable accurate and efficient large-scale IBD detection, we present Parente2, a novel method for detecting IBD segments. Parente2 is based on an embedded log-likelihood ratio and uses a model that accounts for linkage disequilibrium by explicitly modeling haplotype frequencies. Parente2 operates directly on genotype data without the need to phase data prior to IBD inference. We evaluate Parente2's performance through extensive simulations using real data, and we show that it provides substantially higher accuracy compared to previous state-of-the-art methods while maintaining high computational efficiency.
| S-EPMC4315301 | biostudies-literature