{"id":"https://openalex.org/W7204479313","doi":"https://doi.org/10.64898/2026.08.21.26360249","title":"A Framework For Large-Scale Reconstruction Of Extended Pedigrees To Facilitate Gene Discovery In ALS","display_name":"A Framework For Large-Scale Reconstruction Of Extended Pedigrees To Facilitate Gene Discovery In ALS","publication_year":2026,"publication_date":"2026-08-27","ids":{"openalex":"https://openalex.org/W7204479313","doi":"https://doi.org/10.64898/2026.08.21.26360249"},"language":"en","primary_location":{"id":"doi:10.64898/2026.08.21.26360249","doi":"https://doi.org/10.64898/2026.08.21.26360249","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.21.26360249","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/08/27/2026.08.21.26360249.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"volume":null,"type":"preprint","is_traditional":true,"indexed_in":["crossref"],"open_access":{"is_oa":true,"oa_status":"green","oa_url":"https://www.medrxiv.org/content/medrxiv/early/2026/08/27/2026.08.21.26360249.full.pdf","any_repository_has_fulltext":true},"authorships":[{"author_position":"first","author":{"id":"https://openalex.org/A5113278304","display_name":"Daphne van Oosten","orcid":"https://orcid.org/0009-0009-1747-3246","observed_orcids":["https://orcid.org/0009-0009-1747-3246"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Daphne van Oosten","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0009-0009-1747-3246","affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5015233595","display_name":"Paul Beele","orcid":"https://orcid.org/0000-0003-0478-0836","observed_orcids":["https://orcid.org/0000-0003-0478-0836"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Paul Beele","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0003-0478-0836","affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5100582110","display_name":"Bi\u2010Nan Wang","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Bi-nan Wang","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5148431398","display_name":"Sophie J. Plasmans","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Sophie Josephine Plasmans","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5148441088","display_name":"Nienke Wolthuis","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Nienke Wolthuis","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5148455130","display_name":"Kyara van den Berg","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Kyara van den Berg","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5148469842","display_name":"Maaike P. T. Blom","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Maaike Paulina Theodora Blom","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5080970048","display_name":"Myrte Meyjes","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Myrte Meyjes","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5001463791","display_name":"Nina D. van der Schoot","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Nina Dianne van der Schoot","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5051698261","display_name":"Hermieneke Vergunst-Bosch","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Hermieneke Vergunst-Bosch","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5023704901","display_name":"Aim\u00e9e R. Kok","orcid":"https://orcid.org/0000-0002-2728-2795","observed_orcids":["https://orcid.org/0000-0002-2728-2795"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Aim\u00e9e Rosanne Kok","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5148452771","display_name":"Lucas J. van der Ven","orcid":null,"observed_orcids":[]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Lucas Johannes van de Ven","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5075905262","display_name":"Michael A. van Es","orcid":"https://orcid.org/0000-0002-7709-5883","observed_orcids":["https://orcid.org/0000-0002-7709-5883"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Michael A. van Es","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-7709-5883","affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5067571282","display_name":"Leonard H. van den Berg","orcid":"https://orcid.org/0000-0002-5203-9674","observed_orcids":["https://orcid.org/0000-0002-5203-9674","https://orcid.org/0000-0002-6559-3965"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Leonard Hendrik van den Berg","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":null,"affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"middle","author":{"id":"https://openalex.org/A5069816083","display_name":"Jan Herman Veldink","orcid":"https://orcid.org/0000-0001-5572-9657","observed_orcids":["https://orcid.org/0000-0001-5572-9657","https://orcid.org/0000-0002-4010-2357"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":false,"raw_author_name":"Jan Herman Veldink","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0001-5572-9657","affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]},{"author_position":"last","author":{"id":"https://openalex.org/A5074077702","display_name":"Wouter van Rheenen","orcid":"https://orcid.org/0000-0002-5860-1533","observed_orcids":["https://orcid.org/0000-0002-5860-1533"]},"institutions":[{"id":"https://openalex.org/I3018483916","display_name":"University Medical Center Utrecht","ror":"https://ror.org/0575yy874","country_code":"NL","type":"healthcare","lineage":["https://openalex.org/I3018483916"]}],"countries":["NL"],"is_corresponding":true,"raw_author_name":"Wouter van Rheenen","raw_affiliation_strings":["Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands"],"raw_orcid":"https://orcid.org/0000-0002-5860-1533","affiliations":[{"raw_affiliation_string":"Department of Neurology, UMC Utrecht Brain Center, University Medical Center Utrecht, Utrecht, The Netherlands","institution_ids":["https://openalex.org/I3018483916"]}]}],"institutions":[],"countries_distinct_count":1,"institutions_distinct_count":1,"corresponding_author_ids":["https://openalex.org/A5074077702"],"corresponding_institution_ids":["https://openalex.org/I3018483916"],"apc_list":null,"apc_paid":null,"fwci":null,"has_fulltext":true,"cited_by_count":1,"citation_normalized_percentile":null,"cited_by_percentile_year":null,"biblio":{"volume":null,"issue":null,"first_page":null,"last_page":null},"is_retracted":false,"is_paratext":false,"is_xpac":false,"primary_topic":{"id":"https://openalex.org/T10855","display_name":"Amyotrophic Lateral Sclerosis Research","score":0.9911999702453613,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},"topics":[{"id":"https://openalex.org/T10855","display_name":"Amyotrophic Lateral Sclerosis Research","score":0.9911999702453613,"subfield":{"id":"https://openalex.org/subfields/2728","display_name":"Clinical Neurology"},"field":{"id":"https://openalex.org/fields/27","display_name":"Medicine"},"domain":{"id":"https://openalex.org/domains/4","display_name":"Health Sciences"}},{"id":"https://openalex.org/T10261","display_name":"Genetic Associations and Epidemiology","score":0.0027000000700354576,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}},{"id":"https://openalex.org/T11642","display_name":"Genomics and Rare Diseases","score":0.0013000000035390258,"subfield":{"id":"https://openalex.org/subfields/1311","display_name":"Genetics"},"field":{"id":"https://openalex.org/fields/13","display_name":"Biochemistry, Genetics and Molecular Biology"},"domain":{"id":"https://openalex.org/domains/1","display_name":"Life Sciences"}}],"keywords":[{"id":"https://openalex.org/keywords/amyotrophic-lateral-sclerosis","display_name":"amyotrophic lateral sclerosis","score":0.9990000128746033},{"id":"https://openalex.org/keywords/c9orf72-repeat-expansion","display_name":"C9orf72 repeat expansion","score":0.9549999833106995},{"id":"https://openalex.org/keywords/genealogical-records","display_name":"genealogical records","score":0.7870000004768372},{"id":"https://openalex.org/keywords/identity-by-descent","display_name":"identity by descent","score":0.7360000014305115},{"id":"https://openalex.org/keywords/familial-aggregation","display_name":"familial aggregation","score":0.6259999871253967},{"id":"https://openalex.org/keywords/gene-discovery","display_name":"gene discovery","score":0.49300000071525574},{"id":"https://openalex.org/keywords/genetic-diagnosis","display_name":"genetic diagnosis","score":0.5600000023841858},{"id":"https://openalex.org/keywords/phenotypic-similarity","display_name":"phenotypic similarity","score":0.5770000219345093},{"id":"https://openalex.org/keywords/open-source-toolkit","display_name":"open-source software toolkit","score":0.3659999966621399}],"concepts":[{"id":"https://openalex.org/C2777898937","wikidata":"https://www.wikidata.org/wiki/Q5008447","display_name":"C9orf72","level":5,"score":0.7904999852180481},{"id":"https://openalex.org/C22593422","wikidata":"https://www.wikidata.org/wiki/Q3242583","display_name":"Pedigree chart","level":3,"score":0.6919000148773193},{"id":"https://openalex.org/C2780596555","wikidata":"https://www.wikidata.org/wiki/Q206901","display_name":"Amyotrophic lateral sclerosis","level":3,"score":0.6402000188827515},{"id":"https://openalex.org/C2908647359","wikidata":"https://www.wikidata.org/wiki/Q2625603","display_name":"Population","level":2,"score":0.5482000112533569},{"id":"https://openalex.org/C2781179581","wikidata":"https://www.wikidata.org/wiki/Q2857712","display_name":"Family history","level":2,"score":0.5311999917030334},{"id":"https://openalex.org/C31467283","wikidata":"https://www.wikidata.org/wiki/Q912147","display_name":"Genotyping","level":4,"score":0.48089998960494995},{"id":"https://openalex.org/C54355233","wikidata":"https://www.wikidata.org/wiki/Q7162","display_name":"Genetics","level":1,"score":0.4668000042438507},{"id":"https://openalex.org/C86803240","wikidata":"https://www.wikidata.org/wiki/Q420","display_name":"Biology","level":0,"score":0.4129999876022339},{"id":"https://openalex.org/C71924100","wikidata":"https://www.wikidata.org/wiki/Q11190","display_name":"Medicine","level":0,"score":0.37299999594688416},{"id":"https://openalex.org/C72563966","wikidata":"https://www.wikidata.org/wiki/Q1303415","display_name":"Cohort","level":2,"score":0.35910001397132874},{"id":"https://openalex.org/C166252455","wikidata":"https://www.wikidata.org/wiki/Q6736610","display_name":"Trinucleotide repeat expansion","level":4,"score":0.352400004863739},{"id":"https://openalex.org/C78458016","wikidata":"https://www.wikidata.org/wiki/Q840400","display_name":"Evolutionary biology","level":1,"score":0.33739998936653137},{"id":"https://openalex.org/C64474127","wikidata":"https://www.wikidata.org/wiki/Q1071953","display_name":"Medical genetics","level":3,"score":0.33730000257492065},{"id":"https://openalex.org/C64618202","wikidata":"https://www.wikidata.org/wiki/Q3733697","display_name":"Genetic heterogeneity","level":4,"score":0.3361000120639801},{"id":"https://openalex.org/C2779134260","wikidata":"https://www.wikidata.org/wiki/Q12136","display_name":"Disease","level":2,"score":0.3336000144481659},{"id":"https://openalex.org/C32220436","wikidata":"https://www.wikidata.org/wiki/Q2072214","display_name":"Personalized medicine","level":2,"score":0.33230000734329224},{"id":"https://openalex.org/C23131810","wikidata":"https://www.wikidata.org/wiki/Q818574","display_name":"Observational study","level":2,"score":0.3303999900817871},{"id":"https://openalex.org/C61320498","wikidata":"https://www.wikidata.org/wiki/Q265193","display_name":"Microsatellite","level":4,"score":0.32280001044273376},{"id":"https://openalex.org/C80227256","wikidata":"https://www.wikidata.org/wiki/Q1124169","display_name":"Genetic counseling","level":2,"score":0.3224000036716461},{"id":"https://openalex.org/C2780673598","wikidata":"https://www.wikidata.org/wiki/Q285223","display_name":"Genetic testing","level":2,"score":0.3093000054359436},{"id":"https://openalex.org/C70721500","wikidata":"https://www.wikidata.org/wiki/Q177005","display_name":"Computational biology","level":1,"score":0.30889999866485596},{"id":"https://openalex.org/C2777767895","wikidata":"https://www.wikidata.org/wiki/Q4691924","display_name":"Age of onset","level":3,"score":0.28769999742507935},{"id":"https://openalex.org/C534262118","wikidata":"https://www.wikidata.org/wiki/Q177719","display_name":"Medical diagnosis","level":2,"score":0.28610000014305115},{"id":"https://openalex.org/C186413461","wikidata":"https://www.wikidata.org/wiki/Q744727","display_name":"Genetic association","level":5,"score":0.2754000127315521},{"id":"https://openalex.org/C60644358","wikidata":"https://www.wikidata.org/wiki/Q128570","display_name":"Bioinformatics","level":1,"score":0.27219998836517334},{"id":"https://openalex.org/C106208931","wikidata":"https://www.wikidata.org/wiki/Q1098876","display_name":"Genome-wide association study","level":5,"score":0.25450000166893005},{"id":"https://openalex.org/C81977670","wikidata":"https://www.wikidata.org/wiki/Q585259","display_name":"Genetic diversity","level":3,"score":0.25380000472068787},{"id":"https://openalex.org/C47042493","wikidata":"https://www.wikidata.org/wiki/Q265799","display_name":"Human genetics","level":3,"score":0.2535000145435333},{"id":"https://openalex.org/C167135981","wikidata":"https://www.wikidata.org/wiki/Q2146302","display_name":"Retrospective cohort study","level":2,"score":0.2533999979496002}],"mesh":[],"locations_count":1,"locations":[{"id":"doi:10.64898/2026.08.21.26360249","doi":"https://doi.org/10.64898/2026.08.21.26360249","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.21.26360249","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/08/27/2026.08.21.26360249.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"}],"best_oa_location":{"id":"doi:10.64898/2026.08.21.26360249","doi":"https://doi.org/10.64898/2026.08.21.26360249","is_oa":true,"landing_page_url":"https://doi.org/10.64898/2026.08.21.26360249","pdf_url":"https://www.medrxiv.org/content/medrxiv/early/2026/08/27/2026.08.21.26360249.full.pdf","source":{"id":"https://openalex.org/S3005729997","display_name":"medRxiv","issn_l":null,"issn":null,"is_oa":false,"is_in_doaj":false,"is_core":true,"listed_in":["cwts-core"],"host_organization":null,"host_organization_name":null,"host_organization_lineage":["https://openalex.org/P4310315909"],"host_organization_lineage_names":["Cold Spring Harbor Laboratory Press"],"type":"repository"},"license":null,"license_id":null,"version":"submittedVersion","is_accepted":false,"is_published":false,"raw_source_name":"medRxiv","raw_type":"posted-content"},"sustainable_development_goals":[{"id":"https://metadata.un.org/sdg/3","score":0.98580002784729,"display_name":"Good health and well-being"}],"study_designs":[{"id":"https://openalex.org/study-designs/observational-study","display_name":"Observational Study"}],"awards":[],"funders":[{"id":"https://openalex.org/F4320321800","display_name":"Nederlandse Organisatie voor Wetenschappelijk Onderzoek","ror":"https://ror.org/04jsz6e67"}],"has_content":{"pdf":true,"grobid_xml":true},"content_urls":{"pdf":"https://content.openalex.org/works/W7204479313.pdf","grobid_xml":"https://content.openalex.org/works/W7204479313.grobid-xml"},"referenced_works_count":0,"referenced_works":[],"related_works":["https://openalex.org/W7202278820","https://openalex.org/W3118759931","https://openalex.org/W4394602233","https://openalex.org/W4389441897","https://openalex.org/W7214353055","https://openalex.org/W2797975136","https://openalex.org/W2143463699","https://openalex.org/W2530090162","https://openalex.org/W3193048169","https://openalex.org/W2298230460"],"abstract_inverted_index":{"Abstract":[0],"Importance":[1],"With":[2],"emerging":[3],"gene-targeted":[4],"therapies":[5],"in":[6,33,41,81,154,216,262,269,312,336,354,375,460],"amyotrophic":[7],"lateral":[8],"sclerosis":[9],"(ALS),":[10],"gene":[11,56,458],"discoveries":[12],"and":[13,37,62,78,105,110,122,136,149,159,276,314,327,412,462],"genetic":[14,58,79],"diagnoses":[15],"provide":[16,444],"a":[17,137,145,355,365,386,426,445],"crucial":[18],"path":[19],"to":[20,192,224,229,317,350,367,385,448],"treatment.":[21,63],"Pathogenic":[22],"variants":[23,311],"with":[24,92,134,171,176,179,226,236,431],"moderate":[25],"effect":[26],"or":[27],"incomplete":[28],"penetrance,":[29],"however,":[30],"remain":[31],"unidentified":[32],"genome-wide":[34,106],"association":[35],"studies":[36],"can":[38,345],"appear":[39],"sporadic":[40,303],"small":[42,453],"modern-day":[43],"pedigrees.":[44,131],"Lack":[45],"of":[46,48,51,69,72,88,129,167,189,218,233,246,264,280,284,301,308,330,378,388,400],"recognition":[47],"familial":[49],"clustering":[50],"ALS":[52,90,117,135,177,288,379,461],"limits":[53],"opportunities":[54],"for":[55,108,287,457],"discovery,":[57],"diagnosis,":[59],"risk":[60],"counseling,":[61],"Objective":[64],"To":[65],"determine":[66],"the":[67,93,120,165,187,194,230,244,259,291,299,306,324,391,432],"power":[68],"automated":[70,325],"reconstruction":[71,128,283,326],"extended":[73,130,220,285,331,346,369,417,450],"pedigrees,":[74,451],"integrating":[75],"archive":[76],"records":[77,335,377],"relatedness,":[80],"gene-discovery":[82],"studies.":[83],"Design":[84],"Retrospective":[85],"observational":[86],"study":[87],"Dutch":[89,151],"patients":[91,289,389],"C9orf72":[94,139,168,195,209,260,292,392,433],"hexanucleotide":[95],"repeat":[96,393,434],"expansion":[97,435],"(HRE),":[98],"combining":[99],"clinical":[100,146,180,237,409],"family":[101,147,181,238,410],"history,":[102],"civil":[103],"records,":[104],"genotyping":[107],"relatedness":[109],"identity-by-descent":[111],"(IBD)":[112],"inference.":[113],"Setting":[114],"National,":[115],"population-based":[116],"cohort":[118,387],"from":[119,333,371,408],"Netherlands":[121],"digitized":[123],"population":[124,155],"archives":[125,281],"enabling":[126],"systematic":[127],"Participants":[132,141],"Individuals":[133],"confirmed":[138],"HRE.":[140,196,293],"must":[142],"have":[143],"provided":[144],"history":[148,239],"traceable":[150],"ancestry":[152],"documented":[153],"archives.":[156],"Main":[157],"Outcomes":[158],"Measures":[160],"The":[161,183],"primary":[162],"outcome":[163,185],"was":[164,186,436],"proportion":[166],"HRE":[169,210,261],"carriers":[170],"newly":[172],"identified":[173,247,396],"(distant)":[174],"relatives":[175],"compared":[178],"history.":[182],"secondary":[184],"precision":[188],"IBD-based":[190],"methods":[191,384],"fine-map":[193],"Other":[197],"outcomes":[198],"included":[199,215],"phenotypic":[200],"similarities":[201],"between":[202],"distantly":[203],"related":[204],"patients.":[205,380],"Results":[206],"Among":[207],"238":[208],"carriers,":[211],"91":[212],"could":[213,404],"be":[214,348,406],"one":[217],"39":[219],"pedigrees":[221,265,286,332,347,370,418],"dating":[222],"back":[223],"\u223c1800,":[225],"relationships":[227,248],"up":[228],"eighth":[231],"degree":[232],"relatedness.":[234],"Compared":[235],"alone,":[240],"our":[241,383],"approach":[242,297,447],"increased":[243],"number":[245],"by":[249,266,420],"2.5-":[250],"fold.":[251],"Genome-wide":[252],"IBD":[253,273,429],"analysis":[254],"revealed":[255],"shared":[256,428],"haplotypes":[257],"encompassing":[258],"97%":[263],"\u22657":[267,421],"meioses":[268,422],"10.2-127.0":[270],"centimorgans":[271],"total":[272],"shared.":[274],"Conclusions":[275],"Relevance":[277],"Large-scale":[278],"interrogation":[279],"facilitates":[282,305],"carrying":[290,390],"This":[294,395],"combined":[295],"genealogical\u2013genetic":[296],"supports":[298],"reclassification":[300],"apparently":[302],"cases,":[304],"discovery":[307,459],"new":[309],"disease-causing":[310],"ALS,":[313],"is":[315],"generalizable":[316,446],"other":[318,463],"late-onset":[319,356,464],"neurodegenerative":[320,357,465],"diseases.":[321,466],"We":[322,363,381,443],"implemented":[323],"interactive":[328],"visualization":[329],"genealogical":[334,373],"an":[337],"open-source":[338],"software":[339],"toolkit.":[340],"Key":[341],"points":[342],"Question":[343],"How":[344],"leveraged":[349],"identify":[351],"disease":[352,358],"genes":[353],"such":[359],"as":[360],"ALS?":[361],"Findings":[362],"built":[364],"pipeline":[366],"reconstruct":[368,449],"large-scale":[372],"data":[374],"archival":[376],"applied":[382],"expansion.":[394],"67":[397],"distant":[398],"relationships,":[399],"which":[401],"38":[402],"(57%)":[403],"not":[405],"inferred":[407],"histories":[411],"were":[413],"thus":[414],"novel.":[415],"In":[416],"connected":[419],"(N":[423],"=":[424],"35),":[425],"single":[427],"segment":[430],"identified,":[437],"spanning":[438],"only":[439],"10.2-27.0":[440],"centimorgans.":[441],"Meaning":[442],"detecting":[452],"enough":[454],"genomic":[455],"regions":[456]},"counts_by_year":[{"year":2026,"cited_by_count":1}],"updated_date":"2026-11-09T13:22:03.289127","created_date":"2026-08-28T00:00:00"}
