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We tested disease\u2010associated mutation burden in ELLI genomes by determining the burden of pathogenic variants reported in the ClinVar and HGMD databases using data from whole exome sequencing (WES) conducted in a cohort of ELLI, their offspring, and control individuals without antecedents of familial longevity (<jats:italic>n<\/jats:italic>\u00a0=\u00a01879), all descendent from the founder population of Ashkenazi Jews. The burden of pathogenic variants did not differ between the three groups. Additional analyses of variants subtypes and variant effect predictor (VEP) biotype frequencies did not reveal a decrease of pathogenic or loss\u2010of\u2010function (LoF) variants in ELLI and offspring compared to the control group. Case\u2013control pathogenic variants enrichment analyses conducted in ELLI and controls also did not identify significant differences in any of the variants between the groups and polygenic risk scores failed to provide a predictive model. Interestingly, cancer and Alzheimer's disease\u2010associated variants were significantly depleted in ELLI compared to controls, suggesting slower accumulation of mutation. That said, polygenic risk score analysis failed to find any predictive variants among the functional variants tested. The high similarity in the burden of pathogenic variation between ELLI and individuals without familial longevity supports the notion that extension of lifespan and healthspan in ELLI is not a consequence of pathogenic variant depletion but rather a result of other genomic, epigenomic, or potentially nongenomic properties.<\/jats:p>","DOI":"10.1111\/acel.13216","type":"journal-article","created":{"date-parts":[[2020,8,29]],"date-time":"2020-08-29T18:43:38Z","timestamp":1598726618000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":12,"title":["Similar burden of pathogenic coding variants in exceptionally long\u2010lived individuals and individuals without exceptional longevity"],"prefix":"10.1111","volume":"19","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-9761-580X","authenticated-orcid":false,"given":"Danielle","family":"Gutman","sequence":"first","affiliation":[{"name":"Faculty of Natural Sciences University of Haifa  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gabriel","family":"Lidzbarsky","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences University of Haifa  Haifa Israel"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sofiya","family":"Milman","sequence":"additional","affiliation":[{"name":"Department of Medicine Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tina","family":"Gao","sequence":"additional","affiliation":[{"name":"Department of Medicine Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Patrick","family":"Sin-Chan","sequence":"additional","affiliation":[{"name":"Regeneron Genetics Center  Tarrytown New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Claudia","family":"Gonzaga\u2010Jauregui","sequence":"additional","affiliation":[{"name":"Regeneron Genetics Center  Tarrytown New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"name":"Regeneron Genetics Center","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Joris","family":"Deelen","sequence":"additional","affiliation":[{"name":"Max Planck Institute for Biology of Ageing  Cologne Germany"},{"name":"Molecular Epidemiology Department of Biochemical Data Sciences Leiden University Medical Center  Leiden The Netherlands"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alan R.","family":"Shuldiner","sequence":"additional","affiliation":[{"name":"Regeneron Genetics Center  Tarrytown New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nir","family":"Barzilai","sequence":"additional","affiliation":[{"name":"Department of Medicine Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Genetic, Institute for Aging Research and the Diabetes Research Center Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gil","family":"Atzmon","sequence":"additional","affiliation":[{"name":"Faculty of Natural Sciences University of Haifa  Haifa Israel"},{"name":"Department of Medicine Albert Einstein College of Medicine  Bronx New York USA"},{"name":"Genetic, Institute for Aging Research and the Diabetes Research Center Albert Einstein College of Medicine  Bronx New York USA"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"311","published-online":{"date-parts":[[2020,8,29]]},"reference":[{"key":"e_1_2_9_2_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glr223"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1038\/nprot.2010.116"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0906191106"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.2174\/1570161111666131219113544"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1046\/j.1532-5415.2001.49013.x"},{"key":"e_1_2_9_7_1","doi-asserted-by":"publisher","DOI":"10.1111\/acel.12039"},{"key":"e_1_2_9_8_1","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pcbi.0030170"},{"key":"e_1_2_9_9_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajhg.2012.07.017"},{"key":"e_1_2_9_10_1","doi-asserted-by":"publisher","DOI":"10.1093\/gerona\/glu166"},{"key":"e_1_2_9_11_1","doi-asserted-by":"publisher","DOI":"10.1007\/s00439-013-1342-z"},{"key":"e_1_2_9_12_1","doi-asserted-by":"publisher","DOI":"10.1038\/ncomms5835"},{"key":"e_1_2_9_13_1","doi-asserted-by":"publisher","DOI":"10.1186\/s13742-015-0047-8"},{"key":"e_1_2_9_14_1","doi-asserted-by":"publisher","DOI":"10.1093\/gigascience\/giz082"},{"key":"e_1_2_9_15_1","unstructured":"Clayton D.(2020).snpStats: SnpMatrix and XSnpMatrix classes and methods. 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