Comparison of IBD detection methods with a focus on rare variants

Identity by descent (IBD) between two individuals means that both inherited the same DNA sequence from a common ancestor. Detection of IBD tracts is important for population genetics and association studies. IBD detection methods perform well for family studies where pedigrees are available and for common single nucleotide variants (SNVs). However recent genotyping projects utilizing next generation sequencing comprise unrelated individuals and detect mostly rare variants. Currently, rare variants are of high interest in genetics because they are assumed to cause complex human diseases. However their association with a disease is hard to detect as standard tests on rare variants yield low power. IBD mapping can be used to increase the power by two approaches. First, SNVs can be grouped based on IBD and subsequently their joint effect tested for disease association. Secondly, local genetic similarities between individuals can be measured by IBD and used for association tests like implemented in the sequence kernel association test (SKAT). With a focus on rare variants, we compare the two most commonly used IBD detection techniques, BEAGLE’s fastIBD and PLINK, on simulated data with implanted rare IBD tracts. Both methods miss a large proportion of short tracts and tracts that are tagged by few minor alleles. Overall fastIBD has slightly higher power than PLINK while having a higher false discovery rate. fastIBD systematically overestimates the length of IBD tracts while PLINK estimates it well. However the exact location and length of an IBD tract is essential for identifying disease loci by IBD mapping.