PADRE: Pedigree-Aware Distant-Relationship Estimation.

TitlePADRE: Pedigree-Aware Distant-Relationship Estimation.
Publication TypeJournal Article
Year of Publication2016
AuthorsStaples, J, Witherspoon, DJ, Jorde, LB, Nickerson, DA, Below, JE, Huff, CD
Corporate AuthorsUniversity of Washington Center for Mendelian Genomics
JournalAm J Hum Genet
Date Published2016 07 07
KeywordsAlgorithms, Female, Haplotypes, Humans, Male, Models, Genetic, Pedigree, Reproducibility of Results

Accurate estimation of shared ancestry is an important component of many genetic studies; current prediction tools accurately estimate pairwise genetic relationships up to the ninth degree. Pedigree-aware distant-relationship estimation (PADRE) combines relationship likelihoods generated by estimation of recent shared ancestry (ERSA) with likelihoods from family networks reconstructed by pedigree reconstruction and identification of a maximum unrelated set (PRIMUS), improving the power to detect distant relationships between pedigrees. Using PADRE, we estimated relationships from simulated pedigrees and three extended pedigrees, correctly predicting 20% more fourth- through ninth-degree simulated relationships than when using ERSA alone. By leveraging pedigree information, PADRE can even identify genealogical relationships between individuals who are genetically unrelated. For example, although 95% of 13(th)-degree relatives are genetically unrelated, in simulations, PADRE correctly predicted 50% of 13(th)-degree relationships to within one degree of relatedness. The improvement in prediction accuracy was consistent between simulated and actual pedigrees. We also applied PADRE to the HapMap3 CEU samples and report new cryptic relationships and validation of previously described relationships between families. PADRE greatly expands the range of relationships that can be estimated by using genetic data in pedigrees.

Alternate JournalAm. J. Hum. Genet.
PubMed ID27374771
PubMed Central IDPMC5005450
Grant ListR01 GM104390 / GM / NIGMS NIH HHS / United States
U54 HG006493 / HG / NHGRI NIH HHS / United States
UM1 HG006493 / HG / NHGRI NIH HHS / United States