{"database":"GEO","file_versions":[{"headers":{"Content-Type":["application/json"]},"body":{"files":{"Other":["ftp://ftp.ncbi.nlm.nih.gov/geo/series/GSE342nnn/GSE342568/"]},"type":"primary"},"statusCode":"OK","statusCodeValue":200}],"scores":null,"additional":{"omics_type":["Transcriptomics"],"species":["Homo sapiens"],"gds_type":["Expression profiling by high throughput sequencing"],"full_dataset_link":["https://www.ncbi.nlm.nih.gov/geo/query/acc.cgi?acc=GSE342568"],"repository":["GEO"],"entry_type":["GSE"],"additional_accession":[]},"is_claimable":false,"name":"Genetic Architecture of Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD) Risk in Mexican Americans.","description":"Hispanics of Mexican American descent in South Texas show a very high prevalence of MASLD, with some studies reporting rates as high as 50% in adults. However, assessment of genetic risk factors underlying this prevalence is complicated by a high co-occurrence of other metabolic disorders and variable endogenous and exogenous environmental risk factors. To map the genetic architecture of MASLD hepatic steatosis risk, we conducted an epidemiological-scale investigation using human induced pluripotent stem cell (iPSC)-derived hepatocyte cultures from 193 participants in our longitudinal South Texas Family Study (STFS). iPSC-based models offer greater power to map genetic risk factors by experimentally controlling for confounding organismal and environmental factors. We combined transcriptome-wide gene expression analysis with high-content cellular measurements of neutral lipids to define a core hepatic steatosis MASLD phenotype at baseline (vehicle-treated) and following a lipid challenge. The additive genetic heritability of hepatic steatosis measures was 0.44 (p-value = 0.03) at baseline and 0.42 (p-value = 0.03) at post-lipid-challenge. Multivariable linear regression comparing each gene’s expression against hepatic steatosis measures identified 1,070 genes at baseline and 1,229 genes post-lipid challenge, whose expression showed a transcriptome-wide statistically significant association (standardized |β| ≥ 0.24; Bonferroni-corrected p-value ≤ 0.001) with baseline and post-lipid challenge hepatic steatosis measures, respectively. Functional annotation and pathway enrichment analyses of these genes implicated a broad range of hepatocellular functions, mapping an overall genetic architecture of MASLD-associated steatosis risk in Mexican Americans. The genes whose expression was positively correlated with hepatic steatosis measures suggest a direct role of variation in fatty acid (FA) and cholesterol uptake, de novo lipogenesis (DNL), and carbohydrate shunts in hepatic steatosis risk, as well as a cellular stress-associated and high-turnover metabolic state marked by elevated FA-oxidation and ketogenesis. In contrast, the genes whose expression was inversely correlated with hepatic steatosis measures suggest a significant role of the cellular cytoskeleton, hepatocyte epithelial integrity, and endosomal and autophagic clearance machinery in steatosis risk.","dates":{"publication":"2026/09/17"},"accession":"GSE342568","cross_references":{"GSM":["GSM9933249","GSM9933007","GSM9933128","GSM9933129","GSM9933008","GSM9933126","GSM9933247","GSM9933005","GSM9933006","GSM9933127","GSM9933248","GSM9933003","GSM9933124","GSM9933245","GSM9933246","GSM9933004","GSM9933125","GSM9933243","GSM9933001","GSM9933122","GSM9933123","GSM9933244","GSM9933002","GSM9933009","GSM9933120","GSM9933241","GSM9933000","GSM9933121","GSM9933242","GSM9933240","GSM9933117","GSM9933238","GSM9933118","GSM9933239","GSM9933115","GSM9933236","GSM9933116","GSM9933237","GSM9933113","GSM9933234","GSM9933114","GSM9933235","GSM9933232","GSM9933111","GSM9933112","GSM9933233","GSM9933119","GSM9933230","GSM9933110","GSM9933231","GSM9933029","GSM9933269","GSM9933027","GSM9933148","GSM9933149","GSM9933028","GSM9933146","GSM9933267","GSM9933025","GSM9933026","GSM9933147","GSM9933268","GSM9933023","GSM9933144","GSM9933265","GSM9933266","GSM9933024","GSM9933145","GSM9933263","GSM9933021","GSM9933142","GSM9933143","GSM9933264","GSM9933022","GSM9933140","GSM9933261","GSM9933020","GSM9933141","GSM9933262","GSM9933260","GSM9933018","GSM9933139","GSM9933019","GSM9933137","GSM9933258","GSM9933016","GSM9933017","GSM9933138","GSM9933259","GSM9933014","GSM9933135","GSM9933256","GSM9933015","GSM9933136","GSM9933257","GSM9933012","GSM9933133","GSM9933254","GSM9933134","GSM9933255","GSM9933013","GSM9933252","GSM9933010","GSM9933131","GSM9933011","GSM9933132","GSM9933253","GSM9933250","GSM9933130","GSM9933251","GSM9933326","GSM9933205","GSM9933206","GSM9933327","GSM9933203","GSM9933324","GSM9933204","GSM9933325","GSM9933201","GSM9933322","GSM9933323","GSM9933202","GSM9933320","GSM9933200","GSM9933321","GSM9933209","GSM9933207","GSM9933328","GSM9933329","GSM9933208","GSM9933315","GSM9933316","GSM9933313","GSM9933314","GSM9933311","GSM9933312","GSM9933310","GSM9933319","GSM9933317","GSM9933318","GSM9933106","GSM9933227","GSM9933107","GSM9933228","GSM9933104","GSM9933225","GSM9933226","GSM9933105","GSM9933223","GSM9933102","GSM9933103","GSM9933224","GSM9933100","GSM9933221","GSM9933101","GSM9933222","GSM9933229","GSM9933108","GSM9933109","GSM9933340","GSM9933220","GSM9933216","GSM9933337","GSM9933217","GSM9933338","GSM9933335","GSM9933214","GSM9933215","GSM9933336","GSM9933212","GSM9933333","GSM9933213","GSM9933334","GSM9933210","GSM9933331","GSM9933332","GSM9933211","GSM9933218","GSM9933339","GSM9933219","GSM9933330","GSM9933089","GSM9933080","GSM9933087","GSM9933088","GSM9933085","GSM9933086","GSM9933083","GSM9933084","GSM9933081","GSM9933082","GSM9933078","GSM9933199","GSM9933079","GSM9933190","GSM9933197","GSM9933076","GSM9933077","GSM9933198","GSM9933074","GSM9933195","GSM9933075","GSM9933196","GSM9933072","GSM9933193","GSM9933073","GSM9933194","GSM9933070","GSM9933191","GSM9933071","GSM9933192","GSM9933090","GSM9933091","GSM9933098","GSM9933099","GSM9933096","GSM9933097","GSM9933094","GSM9933095","GSM9933092","GSM9933093","GSM9933049","GSM9933289","GSM9933047","GSM9933168","GSM9933169","GSM9933048","GSM9933166","GSM9933287","GSM9933045","GSM9933046","GSM9933167","GSM9933288","GSM9933043","GSM9933164","GSM9933285","GSM9933286","GSM9933044","GSM9933165","GSM9933283","GSM9933041","GSM9933162","GSM9933163","GSM9933284","GSM9933042","GSM9933160","GSM9933281","GSM9933040","GSM9933161","GSM9933282","GSM9933280","GSM9933038","GSM9933159","GSM9933039","GSM9933157","GSM9933278","GSM9933036","GSM9933037","GSM9933158","GSM9933279","GSM9933034","GSM9933155","GSM9933276","GSM9933035","GSM9933156","GSM9933277","GSM9933032","GSM9933153","GSM9933274","GSM9933275","GSM9933033","GSM9933154","GSM9933272","GSM9933030","GSM9933151","GSM9933031","GSM9933152","GSM9933273","GSM9933270","GSM9933150","GSM9933271","GSM9933069","GSM9933067","GSM9933188","GSM9933189","GSM9933068","GSM9933186","GSM9933065","GSM9933066","GSM9933187","GSM9933063","GSM9933184","GSM9933064","GSM9933185","GSM9933061","GSM9933182","GSM9933183","GSM9933062","GSM9933180","GSM9933060","GSM9933181","GSM9933058","GSM9933179","GSM9933059","GSM9933177","GSM9933298","GSM9933056","GSM9933057","GSM9933178","GSM9933299","GSM9933054","GSM9933175","GSM9933296","GSM9933055","GSM9933176","GSM9933297","GSM9933052","GSM9933173","GSM9933294","GSM9933295","GSM9933053","GSM9933174","GSM9933292","GSM9933050","GSM9933171","GSM9933051","GSM9933172","GSM9933293","GSM9933290","GSM9933170","GSM9933291","GSM9932958","GSM9932959","GSM9932956","GSM9932957","GSM9932955","GSM9932974","GSM9932975","GSM9932972","GSM9932973","GSM9932970","GSM9932971","GSM9932978","GSM9932979","GSM9932976","GSM9932977","GSM9932963","GSM9932964","GSM9932961","GSM9932962","GSM9932960","GSM9932969","GSM9932967","GSM9932968","GSM9932965","GSM9932966","GSM9933304","GSM9933305","GSM9933302","GSM9933303","GSM9933300","GSM9933301","GSM9933308","GSM9933309","GSM9933306","GSM9933307","GSM9932996","GSM9932997","GSM9932994","GSM9932995","GSM9932992","GSM9932993","GSM9932990","GSM9932991","GSM9932998","GSM9932999","GSM9932985","GSM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