Estimation of the inbreeding coefficient through use of genomic data

Am J Hum Genet. 2003 Sep;73(3):516-23. doi: 10.1086/378207. Epub 2003 Jul 29.


Many linkage studies are performed in inbred populations, either small isolated populations or large populations with a long tradition of marriages between relatives. In such populations, there exist very complex genealogies with unknown loops. Therefore, the true inbreeding coefficient of an individual is often unknown. Good estimators of the inbreeding coefficient (f) are important, since it has been shown that underestimation of f may lead to false linkage conclusions. When an individual is genotyped for markers spanning the whole genome, it should be possible to use this genomic information to estimate that individual's f. To do so, we propose a maximum-likelihood method that takes marker dependencies into account through a hidden Markov model. This methodology also allows us to infer the full probability distribution of the identity-by-descent (IBD) status of the two alleles of an individual at each marker along the genome (posterior IBD probabilities) and provides a variance for the estimates. We simulate a full genome scan mimicking the true autosomal genome for (1) a first-cousin pedigree and (2) a quadruple-second-cousin pedigree. In both cases, we find that our method accurately estimates f for different marker maps. We also find that the proportion of genome IBD in an individual with a given genealogy is very variable. The approach is illustrated with data from a study of demyelinating autosomal recessive Charcot-Marie-Tooth disease.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Charcot-Marie-Tooth Disease / genetics
  • Computer Simulation
  • Consanguinity*
  • Female
  • Genomics
  • Humans
  • Likelihood Functions
  • Male
  • Pedigree