{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"institution":[{"name":"medRxiv"}],"indexed":{"date-parts":[[2026,1,16]],"date-time":"2026-01-16T11:48:14Z","timestamp":1768564094415,"version":"3.49.0"},"posted":{"date-parts":[[2023,12,22]]},"group-title":"Genetic and Genomic Medicine","reference-count":10,"publisher":"openRxiv","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"accepted":{"date-parts":[[2023,12,22]]},"abstract":"<jats:title>Summary<\/jats:title>\n                <jats:p>\n                  The R644C variant of lamin A is controversial, as it has been linked to multiple phenotypes in familial studies, but has also been identified in apparently healthy volunteers. Here we present data from a large midwestern US cohort showing that this variant associates genetically with hepatic steatosis, and with related traits in additional publicly available datasets, while\n                  <jats:italic>in vitro<\/jats:italic>\n                  testing demonstrated that this variant increased cellular lipid droplet accumulation. Taken together, these data support this\n                  <jats:italic>LMNA<\/jats:italic>\n                  variant\u2019s potential pathogenicity in lipodystrophy and metabolic liver disease.\n                <\/jats:p>","DOI":"10.1101\/2023.12.20.23300290","type":"posted-content","created":{"date-parts":[[2023,12,22]],"date-time":"2023-12-22T06:10:15Z","timestamp":1703225415000},"source":"Crossref","is-referenced-by-count":0,"title":["<i>LMNA<\/i>\n                  R644C associates with hepatic steatosis in a large cohort and increases cellular lipid droplet accumulation\n                  <i>in vitro<\/i>"],"prefix":"10.64898","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0000-5085","authenticated-orcid":false,"given":"Kapil K.","family":"Upadhyay","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Xiaomeng","family":"Du","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Yanhua","family":"Chen","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizabeth K.","family":"Speliotes","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8376-5871","authenticated-orcid":false,"given":"Graham F.","family":"Brady","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"54368","reference":[{"key":"2023122600150718000_2023.12.20.23300290v1.1","doi-asserted-by":"crossref","unstructured":"Cotter TG , et al. Gastroenterology 2020; 1851\u20131864.","DOI":"10.1053\/j.gastro.2020.01.052"},{"key":"2023122600150718000_2023.12.20.23300290v1.2","doi-asserted-by":"crossref","unstructured":"Konerman MA , et al. J Hepatol 2018; 362\u2013375.","DOI":"10.1016\/j.jhep.2017.10.015"},{"key":"2023122600150718000_2023.12.20.23300290v1.3","doi-asserted-by":"crossref","unstructured":"Ajluni N , et al. Clin Endocrinol (Oxf) 2017; 698\u2013707.","DOI":"10.1111\/cen.13311"},{"key":"2023122600150718000_2023.12.20.23300290v1.4","doi-asserted-by":"crossref","unstructured":"Brady GF , et al. Gastroenterology 2018; 1602\u20131619.","DOI":"10.1053\/j.gastro.2018.03.026"},{"key":"2023122600150718000_2023.12.20.23300290v1.5","doi-asserted-by":"crossref","unstructured":"Barrowman J , et al. PLoS One 2012; e32120.","DOI":"10.1371\/journal.pone.0032120"},{"key":"2023122600150718000_2023.12.20.23300290v1.6","doi-asserted-by":"crossref","unstructured":"Lin EW , et al. FASEB J 2020; 9051\u20139073.","DOI":"10.1096\/fj.202000500R"},{"key":"2023122600150718000_2023.12.20.23300290v1.7","doi-asserted-by":"publisher","DOI":"10.1210\/clinem\/dgad606"},{"key":"2023122600150718000_2023.12.20.23300290v1.8","unstructured":"Chen VL , et al. Nat Commun 2021; 816."},{"key":"2023122600150718000_2023.12.20.23300290v1.9","doi-asserted-by":"crossref","unstructured":"Upadhyay KK , et al. J Hepatol 2023; 1226\u20131235.","DOI":"10.1016\/j.jhep.2023.07.036"},{"key":"2023122600150718000_2023.12.20.23300290v1.10","unstructured":"Costanzo MC , et al. Cell Metab 2023; 695\u2013710."}],"container-title":[],"original-title":[],"link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/2023.12.20.23300290","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,1,15]],"date-time":"2026-01-15T19:47:08Z","timestamp":1768506428000},"score":1,"resource":{"primary":{"URL":"http:\/\/medrxiv.org\/lookup\/doi\/10.1101\/2023.12.20.23300290"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,12,22]]},"references-count":10,"URL":"https:\/\/doi.org\/10.1101\/2023.12.20.23300290","relation":{},"subject":[],"published":{"date-parts":[[2023,12,22]]},"subtype":"preprint"}}