Near perfect identification of half sibling versus niece/nephew avuncular pairs without pedigree information or genotyped relatives
Abstract
Motivation: Large-scale genomic biobanks contain thousands of second-degree relatives with missing pedigree metadata. Accurately distinguishing half-sibling (HS) from niece/nephew-avuncular (N/A) pairs--both sharing approximately 25% of the genome--remains a significant challenge. Current SNP-based methods rely on Identical-By-Descent (IBD) segment counts and age differences, but substantial distributional overlap leads to high misclassification rates. There is a critical need for a scalable, genotype-only method that can resolve these "half-degree" ambiguities without requiring observed pedigrees or extensive relative information. Results: We present a novel computational framework that achieves near-complete separation of HS and N/A pairs using only genotype data. Our approach utilizes across-chromosome phasing to derive haplotype-level sharing features that summarize how IBD is distributed across parental homologues. By modeling these features with a Gaussian mixture model (GMM), we demonstrate near-perfect classification accuracy (> 98%) in biobank-scale data. Furthermore, we show that these high-confidence relationship labels can serve as long-range phasing anchors, providing structural constraints that improve the accuracy of across-chromosome homologue assignment. This method provides a robust, scalable solution for pedigree reconstruction and the control of cryptic relatedness in large-scale genomic studies.
02 /Specification & Classification
Click any tag to browse matching papers- Citations
- 0
- Assay
- Research Focus
- Approach
Reproducibility ledger
Nobody has reported trying to reproduce this paper yet. Did you replicate an experiment or run the code? Your report saves the next lab a week.
Sign in to file a reproducibility report.
Related papers
- A rapid, accurate approach to inferring pedigrees in endogamous populations
Cole M Williams, Brooke A. Scelza, … Brenna M. Henn·GeneticsPeer-reviewed·May 20, 2025
- Distinguishing pedigree relationships using multi-way identical by descent sharing and sex-specific genetic maps
Ying Qiao, Jens Sannerud, … Amy L. Williams·The American Journal of Human GeneticsPeer-reviewed·Dec 31, 2020
- Accurate Genome-Wide Phasing from IBD Data
Keith Noto, Luong Ruiz·BMC BioinformaticsPeer-reviewed·Nov 23, 2022
- A Novel Method for Across-Chromosome Phasing without Relative Data
Emmanuel Sapin, Kristen M. Kelly, Matthew C. Keller·BioinformaticsPeer-reviewed·May 1, 2026
- A performance assessment of relatedness inference methods using genome-wide data from thousands of relatives
Monica D. Ramstetter, Thomas D. Dyer, … Amy L. Williams·GeneticsPeer-reviewed·Jul 24, 2017
- Reconstructing parent genomes using siblings and other relatives
Ying Qiao, Ethan M. Jewett, … Amy L. Williams·bioRxiv·May 10, 2024