Dataset Information

Estimation of kinship coefficient in structured and admixed populations using sparse sequencing data.

ABSTRACT: Knowledge of biological relatedness between samples is important for many genetic studies. In large-scale human genetic association studies, the estimated kinship is used to remove cryptic relatedness, control for family structure, and estimate trait heritability. However, estimation of kinship is challenging for sparse sequencing data, such as those from off-target regions in target sequencing studies, where genotypes are largely uncertain or missing. Existing methods often assume accurate genotypes at a large number of markers across the genome. We show that these methods, without accounting for the genotype uncertainty in sparse sequencing data, can yield a strong downward bias in kinship estimation. We develop a computationally efficient method called SEEKIN to estimate kinship for both homogeneous samples and heterogeneous samples with population structure and admixture. Our method models genotype uncertainty and leverages linkage disequilibrium through imputation. We test SEEKIN on a whole exome sequencing dataset (WES) of Singapore Chinese and Malays, which involves substantial population structure and admixture. We show that SEEKIN can accurately estimate kinship coefficient and classify genetic relatedness using off-target sequencing data down sampled to ~0.15X depth. In application to the full WES dataset without down sampling, SEEKIN also outperforms existing methods by properly analyzing shallow off-target data (~0.75X). Using both simulated and real phenotypes, we further illustrate how our method improves estimation of trait heritability for WES studies.

SUBMITTER: Dou J

PROVIDER: S-EPMC5636172 | biostudies-literature | 2017 Sep

REPOSITORIES: biostudies-literature

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Estimation of kinship coefficient in structured and admixed populations using sparse sequencing data.

Dou Jinzhuang J Sun Baoluo B Sim Xueling X Hughes Jason D JD Reilly Dermot F DF Tai E Shyong ES Liu Jianjun J Wang Chaolong C

PLoS genetics 20170929 9

Knowledge of biological relatedness between samples is important for many genetic studies. In large-scale human genetic association studies, the estimated kinship is used to remove cryptic relatedness, control for family structure, and estimate trait heritability. However, estimation of kinship is challenging for sparse sequencing data, such as those from off-target regions in target sequencing studies, where genotypes are largely uncertain or missing. Existing methods often assume accurate geno ...[more]

PMID: 28961250

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Project description:BackgroundEstimation of genetic relatedness, or kinship, is used occasionally for recreational purposes and in forensic applications. While numerous methods were developed to estimate kinship, they suffer from high computational requirements and often make an untenable assumption of homogeneous population ancestry of the samples. Moreover, genetic privacy is generally overlooked in the usage of kinship estimation methods. There can be ethical concerns about finding unknown familial relationships in third-party databases. Similar ethical concerns may arise while estimating and reporting sensitive population-level statistics such as inbreeding coefficients for the concerns around marginalization and stigmatization.ResultsHere, we present SIGFRIED, which makes use of existing reference panels with a projection-based approach that simplifies kinship estimation in the admixed populations. We use simulated and real datasets to demonstrate the accuracy and efficiency of kinship estimation. We present a secure federated kinship estimation framework and implement a secure kinship estimator using homomorphic encryption-based primitives for computing relatedness between samples in two different sites while genotype data are kept confidential. Source code and documentation for our methods can be found at https://doi.org/10.5281/zenodo.7053352.ConclusionsAnalysis of relatedness is fundamentally important for identifying relatives, in association studies, and for estimation of population-level estimates of inbreeding. As the awareness of individual and group genomic privacy is growing, privacy-preserving methods for the estimation of relatedness are needed. Presented methods alleviate the ethical and privacy concerns in the analysis of relatedness in admixed, historically isolated and underrepresented populations.Short abstractGenetic relatedness is a central quantity used for finding relatives in databases, correcting biases in genome wide association studies and for estimating population-level statistics. Methods for estimating genetic relatedness have high computational requirements, and occasionally do not consider individuals from admixed ancestries. Furthermore, the ethical concerns around using genetic data and calculating relatedness are not considered. We present a projection-based approach that can efficiently and accurately estimate kinship. We implement our method using encryption-based techniques that provide provable security guarantees to protect genetic data while kinship statistics are computed among multiple sites.

Project description:The main purpose of this study was to understand the type of dairy cattle that can be optimally used by smallholder farmers in various production environments such that they will maximize their yields without increasing the level of inputs. Anecdotal evidence and previous research suggests that the optimal level of taurine inheritance in crossbred animals lies between 50 and 75% when considering total productivity in tropical management clusters. We set out to assess the relationship between breed composition and productivity for various smallholder production systems in Tanzania. We surveyed 654 smallholder dairy households over a 1-year period and grouped them into production clusters. Based on supplementary feeding, milk productivity and sale as well as household wealth status four clusters were described: low-feed-low-output subsistence, medium-feed-low-output subsistence, maize germ intensive semi-commercial and feed intensive commercial management clusters. About 839 crossbred cows were genotyped at approximately 150,000 single nucleotide polymorphism (SNP) loci and their breed composition determined. Percentage dairyness (proportion of genes from international dairy breeds) was estimated through admixture analysis with Holstein, Friesian, Norwegian Red, Jersey, Guernsey, N'Dama, Gir, and Zebu as references. Four breed types were defined as RED-GUE (Norwegian Red/Friesian-Guernsey; Norwegian Red/Friesian-Jersey), RED-HOL (Norwegian Red/Friesian-Holstein), RED-Zebu (Norwegian Red/Friesian-Zebu), Zebu-RED (Zebu-Norwegian Red/Friesian) based on the combination of breeds that make up the top 76% breed composition. A fixed regression model using a genomic kinship matrix was used to analyze milk yield records. The fitted model accounted for year-month-test-date, parity, age, breed type and the production clusters as fixed effects in the model in addition to random effects of animal and permanent environment effect. Results suggested that RED-Zebu breed type with dairyness between 75 and 85% is the most appropriate for a majority of smallholder management clusters. Additionally, for farmers in the feed intensive management group, animals with a Holstein genetic background with at least 75% dairy composition were the best performing. These results indicate that matching breed type to production management group is central to maximizing productivity in smallholder systems. The findings from this study can serve as a basis to inform the development of the dairy sector in Tanzania and beyond.

Dataset Information

Estimation of kinship coefficient in structured and admixed populations using sparse sequencing data.

Publications

Estimation of kinship coefficient in structured and admixed populations using sparse sequencing data.

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