title: PRIMUS: rapid reconstruction of pedigrees from genome-wide estimates of identity by descent.
abstract: Understanding and correctly utilizing relatedness among samples is essential for genetic analysis; however, managing sample records and pedigrees can often be error prone and incomplete. Data sets ascertained by random sampling often harbor cryptic relatedness that can be leveraged in genetic analyses for maximizing power. We have developed a method that uses genome-wide estimates of pairwise identity by descent to identify families and quickly reconstruct and score all possible pedigrees that fit the genetic data by using up to third-degree relatives, and we have included it in the software package PRIMUS (Pedigree Reconstruction and Identification of the Maximally Unrelated Set). Here, we validate its performance on simulated, clinical, and HapMap pedigrees. Among these samples, we demonstrate that PRIMUS can verify reported pedigree structures and identify cryptic relationships. Finally, we show that PRIMUS reconstructed pedigrees, all of which were previously unknown, for 203 families from a cohort collected in Starr County, TX (1,890 samples).
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA.
authors.forename: Jeffrey
authors.initials: J
authors.lastname: Staples
authors.affiliation: Channing Division of Network Medicine, Harvard School of Public Health, Boston, MA 02115, USA; Department of Biostatistics, Harvard School of Public Health, Boston, MA 02115, USA.
authors.forename: Dandi
authors.initials: D
authors.lastname: Qiao
authors.affiliation: Channing Division of Network Medicine, Harvard School of Public Health, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Michael H
authors.initials: MH
authors.lastname: Cho
authors.affiliation: Channing Division of Network Medicine, Harvard School of Public Health, Boston, MA 02115, USA; Division of Pulmonary and Critical Care Medicine, Brigham and Women's Hospital, Boston, MA 02115, USA.
authors.forename: Edwin K
authors.initials: EK
authors.lastname: Silverman
authors.affiliation: Department of Genome Sciences, University of Washington, Seattle, WA 98195, USA. Electronic address: debnick@uw.edu.
authors.forename: Deborah A
authors.initials: DA
authors.lastname: Nickerson
authors.affiliation: Epidemiology, Human Genetics, & Environmental Sciences, University of Texas Health Science Center, Houston, TX 77225, USA. Electronic address: jennifer.e.below@uth.tmc.edu.
authors.forename: Jennifer E
authors.initials: JE
authors.lastname: Below
mesh_terms: D001483:Base Sequence; D003198:Computer Simulation; D059472:Exome / Q000235:genetics; D005787:Gene Frequency; D005828:Genetics, Population / Q000379:methods*; D006801:Humans; D008969:Molecular Sequence Data; D010375:Pedigree; D029424:Pulmonary Disease, Chronic Obstructive / Q000235:genetics*; D017422:Sequence Analysis, DNA; D012984:Software; D013781:Texas