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Existing tools are designed to identify IBD sharing and leave interpretation and phenotype association tests to further analyses. Here we present Distant Relatedness for Identification and Variant Evaluation (DRIVE) v3, a python command\u2010line interface tool that identifies networks of participants who share an identical haplotype at a given genomic location. Given phenotypic data, DRIVE additionally estimates significant enrichment of dichotomous traits within networks. DRIVE is designed for efficient use across large\u2010scale genetic data resources, featuring a versatile application programming interface and a backend structure designed for flexible integration into existing analytical pipelines. In this work, we describe the implementation of DRIVE v3 and illustrate two applications of the tool to an autosomal dominant condition and to an autosomal recessive condition, cardiomyopathy and cystic fibrosis, respectively. These applications highlight the substantial performance improvements between v1 and v3 and demonstrate practically how the newer features of DRIVE such as the enrichment test can be used in the interpretation of the identified networks.<\/jats:p>","DOI":"10.1002\/gepi.70048","type":"journal-article","created":{"date-parts":[[2026,6,27]],"date-time":"2026-06-27T06:22:07Z","timestamp":1782541327000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["DRIVE v3: Command Line Application for Identity\u2010by\u2010Descent Haplotype Clustering in Large Biobank Scale Data"],"prefix":"10.1002","volume":"50","author":[{"given":"James T.","family":"Baker","sequence":"first","affiliation":[{"name":"Division of Genetic Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hung\u2010Hsin","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Biomedical Sciences Academia Sinica Taipei Taiwan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Grahame F.","family":"Evans","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alyssa C.","family":"Scartozzi","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan J.","family":"Bohlender","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1100-9364","authenticated-orcid":false,"given":"Chad D.","family":"Huff","sequence":"additional","affiliation":[{"name":"University of Texas MD Anderson Cancer Center Houston Texas USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quinn S.","family":"Wells","sequence":"additional","affiliation":[{"name":"Department of Medicine Vanderbilt University Medical Center Nashville Tennessee USA"},{"name":"Vanderbilt Translational and Clinical Cardiovascular Research Center Vanderbilt University School of Medicine Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David C.","family":"Samuels","sequence":"additional","affiliation":[{"name":"Department of Molecular Physiology &amp; Biophysics Vanderbilt University School of Medicine Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1346-1872","authenticated-orcid":false,"given":"Jennifer E.","family":"Below","sequence":"additional","affiliation":[{"name":"Division of Genetic Medicine Vanderbilt University Medical Center Nashville Tennessee USA"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,6,26]]},"reference":[{"key":"e_1_2_8_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btz221"},{"key":"e_1_2_8_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2024.02.015"},{"key":"e_1_2_8_4_1","doi-asserted-by":"publisher","DOI":"10.1534\/genetics.111.136937"},{"key":"e_1_2_8_5_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_2_8_6_1","doi-asserted-by":"publisher","DOI":"10.1093\/ije\/dyaf171"},{"key":"e_1_2_8_7_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giab008"},{"key":"e_1_2_8_8_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioinformatics\/btq126"},{"key":"e_1_2_8_9_1","unstructured":"Dower S.2020.PEP 632 \u2013 Deprecate Distutils Module.https:\/\/peps.python.org\/pep-0632\/#id10."},{"key":"e_1_2_8_10_1","doi-asserted-by":"publisher","DOI":"10.1126\/sciadv.ade7109"},{"key":"e_1_2_8_11_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2025.09.011"},{"key":"e_1_2_8_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41569-024-01074-2"},{"key":"e_1_2_8_13_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2011.04.023"},{"key":"e_1_2_8_14_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.081398.108"},{"key":"e_1_2_8_15_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMoa1110186"},{"key":"e_1_2_8_16_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41588-023-01415-w"},{"key":"e_1_2_8_17_1","doi-asserted-by":"publisher","DOI":"10.1101\/gr.115972.110"},{"key":"e_1_2_8_18_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng1194-216a"},{"key":"e_1_2_8_19_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00424-019-02272-5"},{"key":"e_1_2_8_20_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.2570460"},{"key":"e_1_2_8_21_1","doi-asserted-by":"publisher","DOI":"10.1126\/science.1109557"},{"key":"e_1_2_8_22_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-024-51977-4"},{"key":"e_1_2_8_23_1","doi-asserted-by":"publisher","DOI":"10.1093\/bioadv\/vbae115"},{"key":"e_1_2_8_24_1","doi-asserted-by":"publisher","DOI":"10.1007\/3-540-36557-5_9"},{"key":"e_1_2_8_25_1","doi-asserted-by":"publisher","DOI":"10.1038\/ng0694-169"},{"key":"e_1_2_8_26_1","doi-asserted-by":"publisher","DOI":"10.1038\/s41467-020-19588-x"},{"key":"e_1_2_8_27_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13059-019-1754-8"},{"key":"e_1_2_8_28_1","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCGENETICS.111.000062"},{"key":"e_1_2_8_29_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2015.10.006"},{"key":"e_1_2_8_30_1","doi-asserted-by":"publisher","DOI":"10.7155\/jgaa.00124"},{"key":"e_1_2_8_31_1","doi-asserted-by":"crossref","unstructured":"Raasveldt M. andH.M\u00fchleisen.2019. 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