Benchmarking Relatedness Inference Methods with Genome-Wide Data from Thousands of Relatives

Abstract

Inferring relatedness from genomic data is an essential component of genetic association studies, population genetics, forensics, and genealogy. While numerous methods exist for inferring relatedness, thorough evaluation of these approaches in real data has been lacking. Here, we report an assessment of 12 state-of-the-art pairwise relatedness inference methods using a data set with 2485 individuals contained in several large pedigrees that span up to six generations. We find that all methods have high accuracy (92-99%) when detecting first- and second-degree relationships, but their accuracy dwindles to <43% for seventh-degree relationships. However, most identical by descent (IBD) segment-based methods inferred seventh-degree relatives correct to within one relatedness degree for >76% of relative pairs. Overall, the most accurate methods are Estimation of Recent Shared Ancestry (ERSA) and approaches that compute total IBD sharing using the output from GERMLINE and Refined IBD to infer relatedness. Combining information from the most accurate methods provides little accuracy improvement, indicating that novel approaches, such as new methods that leverage relatedness signals from multiple samples, are needed to achieve a sizeable jump in performance.

Keywords: admixture; identical by descent; relatedness estimation.

Figure 1

Performance comparison of the evaluated methods using the SAMAFS data set. Bar plots denote the percentage of sample pairs that are reported to have a given degree of relatedness and that are inferred to be related as the indicated degree. The bar plots are separated on the horizontal axis by the reported relatedness degree and on the vertical axis by inferred relatedness degree. For clarity, the plots list above each bar the inferred percentage that the corresponding bar depicts. Program names listed in red are IBD segment-based methods while those in black use allele frequencies for inference. Red horizontal bars under a bar plot indicate that the corresponding inferences agree with the reported relationships.