title: Analysis of Latino populations from GALA and MEC studies reveals genomic loci with biased local ancestry estimation.
abstract: BACKGROUND
  Local ancestry analysis of genotype data from recently admixed populations (e.g. Latinos, African Americans) provides key insights into population history and disease genetics. Although methods for local ancestry inference have been extensively validated in simulations (under many unrealistic assumptions), no empirical study of local ancestry accuracy in Latinos exists to date. Hence, interpreting findings that rely on local ancestry in Latinos is challenging.
  
  
  RESULTS
  Here, we use 489 nuclear families from the mainland USA, Puerto Rico and Mexico in conjunction with 3204 unrelated Latinos from the Multiethnic Cohort study to provide the first empirical characterization of local ancestry inference accuracy in Latinos. Our approach for identifying errors does not rely on simulations but on the observation that local ancestry in families follows Mendelian inheritance. We measure the rate of local ancestry assignments that lead to Mendelian inconsistencies in local ancestry in trios (MILANC), which provides a lower bound on errors in the local ancestry estimates. We show that MILANC rates observed in simulations underestimate the rate observed in real data, and that MILANC varies substantially across the genome. Second, across a wide range of methods, we observe that loci with large deviations in local ancestry also show enrichment in MILANC rates. Therefore, local ancestry estimates at such loci should be interpreted with caution. Finally, we reconstruct ancestral haplotype panels to be used as reference panels in local ancestry inference and show that ancestry inference is significantly improved by incoroprating these reference panels.
  
  
  METHODS
  We provide the reconstructed reference panels together with the maps of MILANC rates as a public resource for researchers analyzing local ancestry in Latinos at http://bogdanlab.pathology.ucla.edu
  
  
  BACKGROUND
  Supplementary data are available at Bioinformatics online.
authors.affiliation: Department of Pathology and Molecular Medicine, Geffen School of Medicine, University of California-Los Angeles, CA 10833, USA. R01 HG006399
authors.forename: Bogdan
authors.initials: B
authors.lastname: Pasaniuc
authors.forename: Sriram
authors.initials: S
authors.lastname: Sankararaman
authors.forename: Dara G
authors.initials: DG
authors.lastname: Torgerson
authors.forename: Christopher
authors.initials: C
authors.lastname: Gignoux
authors.forename: Noah
authors.initials: N
authors.lastname: Zaitlen
authors.forename: Celeste
authors.initials: C
authors.lastname: Eng
authors.forename: William
authors.initials: W
authors.lastname: Rodriguez-Cintron
authors.forename: Rocio
authors.initials: R
authors.lastname: Chapela
authors.forename: Jean G
authors.initials: JG
authors.lastname: Ford
authors.forename: Pedro C
authors.initials: PC
authors.lastname: Avila
authors.forename: Jose
authors.initials: J
authors.lastname: Rodriguez-Santana
authors.forename: Gary K
authors.initials: GK
authors.lastname: Chen
authors.forename: Loic
authors.initials: L
authors.lastname: Le Marchand
authors.forename: Brian
authors.initials: B
authors.lastname: Henderson
authors.forename: David
authors.initials: D
authors.lastname: Reich
authors.forename: Christopher A
authors.initials: CA
authors.lastname: Haiman
authors.forename: Esteban
authors.initials: E
authors.lastname: Gonzàlez Burchard
authors.forename: Eran
authors.initials: E
authors.lastname: Halperin
mesh_terms: D015982:Bias; D015331:Cohort Studies; D005190:Family; D056426:Genetic Loci; D005828:Genetics, Population / Q000379:methods; D015894:Genome, Human; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006630:Hispanic or Latino / Q000235:genetics*; D006801:Humans; D017058:Mexican Americans; D011647:Puerto Rico / Q000208:ethnology; D014481:United States / Q000208:ethnology