Dataset Information

Model-free Estimation of Recent Genetic Relatedness.

ABSTRACT: Genealogical inference from genetic data is essential for a variety of applications in human genetics. In genome-wide and sequencing association studies, for example, accurate inference on both recent genetic relatedness, such as family structure, and more distant genetic relatedness, such as population structure, is necessary for protection against spurious associations. Distinguishing familial relatedness from population structure with genotype data, however, is difficult because both manifest as genetic similarity through the sharing of alleles. Existing approaches for inference on recent genetic relatedness have limitations in the presence of population structure, where they either (1) make strong and simplifying assumptions about population structure, which are often untenable, or (2) require correct specification of and appropriate reference population panels for the ancestries in the sample, which might be unknown or not well defined. Here, we propose PC-Relate, a model-free approach for estimating commonly used measures of recent genetic relatedness, such as kinship coefficients and IBD sharing probabilities, in the presence of unspecified structure. PC-Relate uses principal components calculated from genome-screen data to partition genetic correlations among sampled individuals due to the sharing of recent ancestors and more distant common ancestry into two separate components, without requiring specification of the ancestral populations or reference population panels. In simulation studies with population structure, including admixture, we demonstrate that PC-Relate provides accurate estimates of genetic relatedness and improved relationship classification over widely used approaches. We further demonstrate the utility of PC-Relate in applications to three ancestrally diverse samples that vary in both size and genealogical complexity.

SUBMITTER: Conomos MP

PROVIDER: S-EPMC4716688 | biostudies-literature | 2016 Jan

REPOSITORIES: biostudies-literature

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Publications

Model-free Estimation of Recent Genetic Relatedness.

Conomos Matthew P MP Reiner Alexander P AP Weir Bruce S BS Thornton Timothy A TA

American journal of human genetics 20160101 1

Genealogical inference from genetic data is essential for a variety of applications in human genetics. In genome-wide and sequencing association studies, for example, accurate inference on both recent genetic relatedness, such as family structure, and more distant genetic relatedness, such as population structure, is necessary for protection against spurious associations. Distinguishing familial relatedness from population structure with genotype data, however, is difficult because both manifest ...[more]

PMID: 26748516

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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.

Dataset Information

Model-free Estimation of Recent Genetic Relatedness.

Publications

Model-free Estimation of Recent Genetic Relatedness.

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