A likelihood ratio approach for identifying three-quarter siblings in genetic databases
The detection of family relationships in genetic databases is of interest in various scientific disciplines such as genetic epidemiology, population and conservation genetics, forensic science, and genealogical research. Nowadays, screening genetic databases for related individuals forms an important aspect of standard quality control procedures. Relatedness research is usually based on an allele sharing analysis of identity by state (IBS) or identity by descent (IBD) alleles. Existing IBS/IBD methods mainly aim to identify first-degree relationships (parent–offspring or full siblings) and second degree (half-siblings, avuncular, or grandparent–grandchild) pairs. Little attention has been paid to the detection of in-between first and second-degree relationships such as three-quarter siblings (3/4S) who share fewer alleles than first-degree relationships but more alleles than second-degree relationships. With the progressively increasing sample sizes used in genetic research, it becomes more likely that such relationships are present in the database under study. In this paper, we extend existing likelihood ratio (LR) methodology to accurately infer the existence of 3/4S, distinguishing them from full siblings and second-degree relatives. We use bootstrap confidence intervals to express uncertainty in the LRs. Our proposal accounts for linkage disequilibrium (LD) by using marker pruning, and we validate our methodology with a pedigree-based simulation study accounting for both LD and recombination. An empirical genome-wide array data set from the GCAT Genomes for Life cohort project is used to illustrate the method. ; This work was partially supported by grants RTI2018-095518-B-C22 (JG), RTI2018-095518-B-C21 (IGF and CBV), and ADE 10/00026 (RdC) (MCIU/AEI/FEDER) of the Spanish Ministry of Science, Innovation and Universities and the European Regional Development Fund, by grants SGR1269 and 2017 SGR529 (RdC) of the Generalitat de Catalunya, by grant R01 GM075091 (JG) from the United States National Institutes of Health, by the Ramon y Cajal action RYC-2011-07822 (RdC), by Agency for Management of University and Research Grants (AGAUR) of the Catalan Government grant 2017SGR723 (VM), and by the Spanish Association Against Cancer (AECC) Scientific Foundation, grant GCTRA18022MORE (VM). ; Peer Reviewed ; Postprint (published version)