Automatic detection of n-degree family members
Family-based genetic studies often require the identification of relatives up to a specified degree, but existing tools are either restricted to second-degree relatives, return entire connected pedigrees, or require multiple pre- or post-processing steps. We implemented five new functions, namely, <i>prepare_graph, get_kinship, graph_to_trio, get_relations</i>, and <i>Relation_per_proband_plot,</i> in the R package LTFHPlus to address these limitations. <i>prepare_graph</i> constructs a directed graph from population-level trio data using the <i>igraph</i> package and supports attaching additional attributes to individuals. From this graph, relatives of arbitrary degree can be identified efficiently. <i>get_kinship</i> calculates a kinship matrix for all individuals in a (sub)graph, and <i>graph_to_trio</i> reconstructs trio information from identified families, enabling downstream use with other pedigree tools. In addition, familial relations can be labelled from the graph using the function <i>get_relations</i>, and the total and average of each relation per proband can be plotted using <i>Relation_per_proband_plot</i>. Using the publicly available minnbreast dataset, we constructed a graph containing 28,081 individuals and 30,720 familial edges. Across 1,000 repetitions, the median run-time for identifying all relatives up to the third degree for 500 randomly selected individuals was 0.03 s, and kinship matrix calculation had a median run-time of 1.57 s (single-threaded execution). These functions provide a reproducible, scalable, and interoperable solution for integrating family information into genetic analyses.
Authors
- Jette Steinbach (ORCID: https://orcid.org/0000-0003-0553-6480)
- Carsten Bøcker Pedersen (ORCID: https://orcid.org/0000-0003-2077-8533)
- Andrew J. Schork (ORCID: https://orcid.org/0000-0003-4164-9335)
- Florian Privé (ORCID: https://orcid.org/0000-0002-3138-2078)
- Morten Dybdahl Krebs (ORCID: https://orcid.org/0000-0002-4452-0732)
- Bjarni Jóhann Vilhjálmsson (ORCID: https://orcid.org/0000-0003-2277-9249)
- Emil M. Pedersen (ORCID: https://orcid.org/0000-0002-3257-5269)
Institutions
- Broad Institute (US)
- Aarhus University (DK)
- Copenhagen University Hospital (DK)
- Lundbeck Foundation (DK)
Publication Details
- Journal
- Frontiers in Genetics
- Published
- 2025-12-12
- DOI
- https://doi.org/10.3389/fgene.2025.1708315
- Primary Topic
- Genetic Associations and Epidemiology
- Type
- article
- Field-Weighted Citation Impact
- 0.00