In practice, haplotype imputation is done in two steps. The first step involves using LRP to simultaneously phase typed individuals and to identify haplotypes that are IBD. The second step overlays this information on the pedigree. Based on how individuals sharing a haplotype IBD are related, it can then be inferred that some untyped individuals must also carry the haplotype. The following example (Fig. 5) highlights how the second step works. The proband (P) is a deceased lung cancer patient. One of his children (C1) and 10 of his grandchildren (GC1 to GC10) are chip-typed. His legacy coefficient is 0.89. Here we focus on a region around the nicotinic acetylcholine receptor genes on 15q25 where variants, including allele T of SNP rs1051730, were recently shown to associate with smoking behaviour, lung cancer, and peripheral arterial disease17-20. As detailed in the figure legend, there are many sources of information from the pedigree that allowed us to impute HA and HB, two phased haplotypes composed of 1001 consecutive SNPs centred at rs1051730, into P. In particular, we know that P is homozygous TT for rs1051730.
