Summary: Genotype imputation is a key step in the analysis of genome-wide association studies. Upcoming very large reference panels, such as those from The 1000 Genomes Project and the Haplotype Consortium, will improve imputation quality of rare and less common variants, but will also increase the computational burden. Here, we demonstrate how the application of software engineering techniques...

We demonstrate the flexibility of identity-by-descent (IBD) graphs for genotype imputation and testing relationships between genotype and phenotype. We analyzed chromosome 3 and the first replicate of simulated diastolic blood pressure. IBD graphs were obtained from complete pedigrees and full multipoint marker analysis, facilitating subsequent linkage and other analyses. For rare alleles, pedi...

We consider the problem of case-control association testing in samples that contain related individuals, where we assume the pedigree structure is known. Typically, for each marker tested, some individuals will have missing genotype data. The MQLS method has been proposed for association testing in this situation. We show that the MQLS method is equivalent to an approach in which missing genoty...

We present a Bayesian nonparametric model for genetic sequence data in which a set of genetic sequences is modelled using a Markov model of partitions. The partitions at consecutive locations in the genome are related by the splitting and merging of their clusters. Our model can be thought of as a discrete analogue of the continuous fragmentation-coagulation process [Teh et al 2011], preserving...

Genotype imputation, used in genome-wide association studies to expand coverage of single nucleotide polymorphisms (SNPs), has performed poorly in African Americans compared to less admixed populations. Overall, imputation has typically relied on HapMap reference haplotype panels from Africans (YRI), European Americans (CEU), and Asians (CHB/JPT). The 1000 Genomes project offers a wider range o...