The variance of identity-by-descent sharing in the Wright-Fisher model
Genetics, (декабря 2012)DOI: 10.1534/genetics.112.147215
Аннотация
Widespread sharing of long, identical-by-descent (IBD) genetic segments is a
hallmark of populations that have experienced a recent bottleneck. The
detection of these IBD segments is now feasible, enabling a wide range of
applications from phasing and imputation to demographic inference. Here, we
study the distribution of IBD sharing in the Wright-Fisher model. Using
coalescent theory, we calculate the mean and variance of the total sharing
between arbitrary pairs of individuals. We then study the cohort-averaged
sharing: the average total sharing between one individual to the rest of the
cohort. We find that for large cohorts, the cohort-averaged sharing is
distributed approximately normally. Surprisingly, the variance of this
distribution remains large even for large cohorts, implying the existence of
"hyper-sharing" individuals. The presence of such individuals bears important
consequences to the design of sequencing studies, since, if they are selected
for whole-genome sequencing, a larger fraction of the cohort can be
subsequently imputed. We calculate the expected gain in power of imputation by
IBD, and subsequently, in power to detect an association, when individuals are
either randomly selected or are specifically the hyper-sharing individuals.
Finally, we study the distribution of pairwise sharing and cohort-averaged
sharing in the Ashkenazi Jewish population.