{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,4,4]],"date-time":"2026-04-04T04:31:10Z","timestamp":1775277070094,"version":"3.50.1"},"posted":{"date-parts":[[2023,11,20]]},"group-title":"Genetic and Genomic Medicine","reference-count":39,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,11,20]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                <jats:p>\n                  Focal segmental glomerulosclerosis (FSGS) is a common cause of nephrotic syndrome with an annual incidence in the United States in African-Americans compared to European-Americans of 24 cases and 5 cases per million, respectively. Among glomerular diseases in Europe and Latin-America, FSGS was the second most frequent diagnosis, and in Asia the fifth. We expand previous efforts in understanding genetics of FSGS by performing a case-control study involving ethnically-diverse groups FSGS cases (726) and a pool of controls (13,994), using panel sequencing of approximately 2,500 podocyte-expressed genes. Through rare variant association tests, we replicated known risk genes \u2013\n                  <jats:italic>KANK1<\/jats:italic>\n                  ,\n                  <jats:italic>COL4A4,<\/jats:italic>\n                  and\n                  <jats:italic>APOL1<\/jats:italic>\n                  . A novel significant association was observed for the gene encoding complement receptor 1 (\n                  <jats:italic>CR1)<\/jats:italic>\n                  . High-risk rare variants in\n                  <jats:italic>CR1<\/jats:italic>\n                  in the European-American cohort were commonly observed in Latin-and African-Americans. Therefore, a combined rare and common variant analysis was used to replicate the\n                  <jats:italic>CR1<\/jats:italic>\n                  association in non-European populations. The\n                  <jats:italic>CR1<\/jats:italic>\n                  risk variant, rs17047661, gives rise to the Sl1\/Sl2 (R1601G) allele that was previously associated with protection against cerebral malaria. Pleiotropic effects of rs17047661 may explain the difference in allele frequencies across continental ancestries and suggest a possible role for genetically-driven alterations of adaptive immunity in the pathogenesis of FSGS.\n                <\/jats:p>","DOI":"10.1101\/2023.11.20.23298462","type":"posted-content","created":{"date-parts":[[2023,11,21]],"date-time":"2023-11-21T01:15:33Z","timestamp":1700529333000},"source":"Crossref","is-referenced-by-count":2,"title":["<i>CR1<\/i>\n                  variants contribute to FSGS susceptibility across multiple populations"],"prefix":"10.64898","author":[{"given":"Rostislav","family":"Skitchenko","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Zora","family":"Modrusan","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexander","family":"Loboda","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Jeffrey B.","family":"Kopp","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Cheryl A.","family":"Winkler","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Alexey","family":"Sergushichev","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Namrata","family":"Gupta","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Christine","family":"Stevens","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mark J.","family":"Daly","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Andrey","family":"Shaw","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Mykyta","family":"Artomov","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023112307300508000_2023.11.20.23298462v1.1","doi-asserted-by":"crossref","first-page":"661","DOI":"10.1093\/ndt\/gfx189","article-title":"Glomerular disease frequencies by race, sex and region: results from the International Kidney Biopsy Survey","volume":"33","year":"2018","journal-title":"Nephrol. 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