{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,14]],"date-time":"2026-08-14T11:01:37Z","timestamp":1786705297989,"version":"build-2736575974"},"reference-count":25,"publisher":"Wiley","issue":"3","license":[{"start":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T00:00:00Z","timestamp":1699401600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100001411","name":"Indian Council of Medical Research","doi-asserted-by":"publisher","award":["54\/01\/2020\u2010HUM\/BMS"],"award-info":[{"award-number":["54\/01\/2020\u2010HUM\/BMS"]}],"id":[{"id":"10.13039\/501100001411","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J of Gastro and Hepatol"],"published-print":{"date-parts":[[2024,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:sec><jats:title>Background\/Purpose<\/jats:title><jats:p>Genome\u2010wide association studies have reported the association of common variants with nonalcoholic fatty liver disease in genes, namely, <jats:italic>PNPLA3\/TM6SF2\/MBOAT7\/HSD17B13<\/jats:italic>, across ethnicities. However, the approach does not identify rarer variants with a higher effect size. We therefore sequenced the complete exonic regions of patients with nonalcoholic steatohepatitis and controls to compare rare and common variants with a role in the pathogenesis.<\/jats:p><\/jats:sec><jats:sec><jats:title>Methods<\/jats:title><jats:p>This is a prospective study that recruited 54 individuals with\/without fatty infiltration. Patients with biopsy\u2010proven nonalcoholic steatohepatitis and persistently elevated liver enzymes were included. Controls were with normal CT\/MR fat fraction. DNA was isolated from whole blood, amplified (SureSelect<jats:sup>XT<\/jats:sup> Human All Exon V5\u00a0+\u00a0UTR kit) and sequenced (Illumina). Data were filtered for quality, aligned (hg19), and annotated (OpenCRAVAT). Pathogenic (Polyphen\u20102\/SIFT\/ClinVar) variants and variants reported to be associated with NAFLD based on published literature were extracted from our data and compared between patients and controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Results<\/jats:title><jats:p>The mean age of controls (<jats:italic>N<\/jats:italic>\u00a0=\u00a017) and patients (<jats:italic>N<\/jats:italic>\u00a0=\u00a037) was 46.88\u00a0\u00b1\u00a06.94 and 37.46\u00a0\u00b1\u00a013.34\u00a0years, respectively. A total of 251 missense variants out of 89\u2009286 were classified as pathogenic. Of these, 106 (42.23%) were unique to the patients and remaining (<jats:italic>n<\/jats:italic>\u00a0=\u00a0145; 57.77%) were found in both patients and controls. Majority (25\/37; 67.57%) patients had a minimum of one or more rare pathogenic variant(s) related to liver pathology that was not seen in the controls.<\/jats:p><\/jats:sec><jats:sec><jats:title>Conclusion<\/jats:title><jats:p>Elucidating the contribution of rare pathogenic variants would enhance our understanding of the pathogenesis. Including the rarer genes in the polygenic risk scores would enhance prediction power.<\/jats:p><\/jats:sec>","DOI":"10.1111\/jgh.16394","type":"journal-article","created":{"date-parts":[[2023,11,8]],"date-time":"2023-11-08T23:54:18Z","timestamp":1699487658000},"page":"587-595","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Comparing rare variants versus common in the pathogenesis of nonalcoholic fatty liver disease: a whole exome sequencing approach"],"prefix":"10.1111","volume":"39","author":[{"given":"Govardhan","family":"Bale","sequence":"first","affiliation":[{"name":"Asian Healthcare Foundation  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1240-1675","authenticated-orcid":false,"given":"Anand V","family":"Kulkarni","sequence":"additional","affiliation":[{"name":"AIG Hospitals  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nagaraja Rao","family":"Padaki","sequence":"additional","affiliation":[{"name":"AIG Hospitals  Hyderabad Telangana India"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"P. 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