Reducing pervasive false-positive identical-by-descent segments detected by large-scale pedigree analysis

Molecular Biology and Evolution
Eric Y DurandCory Y McLean


Analysis of genomic segments shared identical-by-descent (IBD) between individuals is fundamental to many genetic applications, from demographic inference to estimating the heritability of diseases, but IBD detection accuracy in nonsimulated data is largely unknown. In principle, it can be evaluated using known pedigrees, as IBD segments are by definition inherited without recombination down a family tree. We extracted 25,432 genotyped European individuals containing 2,952 father-mother-child trios from the 23andMe, Inc. data set. We then used GERMLINE, a widely used IBD detection method, to detect IBD segments within this cohort. Exploiting known familial relationships, we identified a false-positive rate over 67% for 2-4 centiMorgan (cM) segments, in sharp contrast with accuracies reported in simulated data at these sizes. Nearly all false positives arose from the allowance of haplotype switch errors when detecting IBD, a necessity for retrieving long (>6 cM) segments in the presence of imperfect phasing. We introduce HaploScore, a novel, computationally efficient metric that scores IBD segments proportional to the number of switch errors they contain. Applying HaploScore filtering to the IBD data at a precision of 0.8 produc...Continue Reading


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