International Biometric Society
INFERRING IDENTITY-BY-DESCENT GENOME SEGMENTS IN ADMIXED POPULATIONS
E. A. Thompson and M.K.Kuhner
University of Washington, Seattle, USA
Individuals who have recent common ancestors may share segments of their
genomes identical by descent (IBD). Since IBD genome is, with high probability, of
the same allelic type, IBD is key to analyses of genetic effects underlying similarities
among related individuals. Traditionally, pedigree-based probabilities of IBD were
used to provide measured of relatedness in the form of an expectation of the
proportion of genome shared IBD by individuals. However, the realized proportion
has high variance, and many have focused on the use modern dense genetic
marker (SNP) data to infer realized IBD proportions. Our focus is on detecting
localized segments of genome shared IBD among related individuals. Our previous
work [1] has shown good performance in detecting IBD segments in homogeneous
populations with low linkage disequilibrium (LD) among the markers used for
inference. We have also shown [2] that detection of excess IBD in cases over a
gene region can provide a signal for a causal locus with multiple rare causal alleles.
Through a study of a simulated population of 20,000 individuals over 50 generations
we are investigating the effect of using inferred IBD on genetic analyses of
heritability of quantitative traits with various underlying genetic architectures,
including traits with rare variant allelic heterogeneity among individuals of different
ethnic origins. However, IBD estimation in a population with both demographic (e.g.
admixture) and genetic (i.e. LD) structure may have high uncertainty.
The focus of this current paper is thus a development of model-based methods for
inferring IBD segments in an admixed population using common SNP variation in the
genotypes of diploid individuals. Segments of haplotype with identity of ethnic origin
(IEO) show broad similarity, but those that are IBD from common ancestors within
the recent history of the population show much higher levels of identity. At any basepair location IBD is embedded within IEO, but segments of IBD can cross junction
boundaries between genome segments of different ethnic origins, due to admixed
common ancestors. In our applications of interest, the time-depth of coancestry
(IBD) of interest is comparable to the time-depth of admixture (IEO), so that the
lengths of IEO segments in the chromosomes of an individual are comparable to
those of IBD sharing between individuals. We use paired hidden Markov models
(HMM) for IEO and IBD to resolve observed haplotypic similarities in the population.
[1] Brown, M. D., Glazner, C. G., Zheng, C., and Thompson, E. A. (2012) Inferring
coancestry in population samples in the presence of linkage disequilibrium.
Genetics, 190: 1447-1460.
[2] Browning, S. G. and Thompson, E. A. (2012) Detecting rare variant associations
by identity by descent mapping in case-control studies. Genetics, 190: 1521-1531.
International Biometric Conference, Florence, ITALY, 6 – 11 July 2014