TY - JOUR
T1 - PADRE
T2 - Pedigree-Aware Distant-Relationship Estimation
AU - Staples, Jeffrey
AU - Witherspoon, David J.
AU - Jorde, Lynn B.
AU - Nickerson, Deborah A.
AU - Below, Jennifer E.
AU - Huff, Chad D.
N1 - Funding Information:
We thank Lauren Petty for her helpful comments on the manuscript. J.S. was supported by the National Science Foundation Graduate Research Fellowship under grant DGE-0718124. D.A.N. was supported by the University of Washington Center for Mendelian Genomics (UW-CMG), funded by the National Human Genome Research Institute and the National Heart, Lung and Blood Institute, grant U54HG006493. C.D.H. was supported by R01 GM104390.
Publisher Copyright:
© 2016 American Society of Human Genetics
PY - 2016/7/7
Y1 - 2016/7/7
N2 - 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 13th-degree relatives are genetically unrelated, in simulations, PADRE correctly predicted 50% of 13th-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.
AB - 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 13th-degree relatives are genetically unrelated, in simulations, PADRE correctly predicted 50% of 13th-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.
KW - genetic analysis
KW - pedigree reconstruction
KW - relatedness estimation
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U2 - 10.1016/j.ajhg.2016.05.020
DO - 10.1016/j.ajhg.2016.05.020
M3 - Article
C2 - 27374771
AN - SCOPUS:84978539298
SN - 0002-9297
VL - 99
SP - 154
EP - 162
JO - American journal of human genetics
JF - American journal of human genetics
IS - 1
ER -