A rapid accurate approach to inferring pedigrees in endogamous populations
Accurate reconstruction of pedigrees from genetic data remains a challenging problem. Many relationship categories (e.g. half-sibships vs avuncular) can be difficult to distinguish without external information. Pedigree inference algorithms are often trained on European-descent families in urban locations. Thus, existing methods tend to perform poorly in endogamous populations for which there may be reticulations within the pedigrees and elevated haplotype sharing. We present a simple, rapid algorithm which initially uses only high-confidence first-degree relationships to seed a machine learning step based on summary statistics of identity-by-descent sharing. One of these statistics, our "haplotype score," is novel and can be used to: (1) distinguish half-sibling pairs from avuncular or grandparent-grandchildren pairs; and (2) assign individuals to ancestor vs descendant generation. We test our approach in a sample of 700 individuals from northern Namibia, sampled from an endogamous population called the Himba. Due to a culture of concurrent relationships in the Himba, there is a high proportion of half-sibships. We accurately identify first through fourth-degree relationships and distinguish between various second-degree relationships: half-sibships, avuncular pairs, and grandparent-grandchildren. We further validate our approach in a second African-descent dataset, the Barbados Asthma Genetics Study, and a European-descent founder population from Quebec. Accurate reconstruction of relatives facilitates estimation of allele frequencies, tracing allele trajectories, improved phasing, heritability and other population genomic questions.
Authors
- Brenna M. Henn (ORCID: https://orcid.org/0000-0003-4998-287X)
- Kathleen C. Barnes (ORCID: https://orcid.org/0000-0002-3030-4705)
- Sohini Ramachandran (ORCID: https://orcid.org/0000-0002-9588-7964)
- Brooke A. Scelza (ORCID: https://orcid.org/0000-0001-5875-8875)
- Harold Watson
- Randi K. Johnson (ORCID: https://orcid.org/0000-0001-9345-4439)
- Neus Font‐Porterias (ORCID: https://orcid.org/0000-0002-1357-9096)
- Ethan M. Lange (ORCID: https://orcid.org/0000-0001-7075-4287)
- Sarah Danielle Slack (ORCID: https://orcid.org/0000-0002-0559-3138)
- Rasika A. Mathias (ORCID: https://orcid.org/0000-0002-2282-9042)
- Dana R. Al-Hindi
- Christopher R. Gignoux (ORCID: https://orcid.org/0000-0001-9728-6567)
- Cole M Williams (ORCID: https://orcid.org/0000-0002-5888-5994)
Institutions
- University of California, Los Angeles (US)
- Brown University (US)
- National Institute of Allergy and Infectious Diseases (US)
- Queen Elizabeth Hospital (BB)
- University of Colorado Anschutz Medical Campus (US)
- University of California, Davis (US)
Publication Details
- Journal
- Genetics
- Published
- 2025-05-20
- DOI
- https://doi.org/10.1093/genetics/iyaf094
- Citations
- 4
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 7.27