dc.contributor.author | Wagschal, Alexandre | |
dc.contributor.author | Najafi-Shoushtari, S Hani | |
dc.contributor.author | Wang, Lifeng | |
dc.contributor.author | Goedeke, Leigh | |
dc.contributor.author | Sinha, Sumita | |
dc.contributor.author | deLemos, Andrew S | |
dc.contributor.author | Black, Josh C | |
dc.contributor.author | Ramírez, Cristina M | |
dc.contributor.author | Li, Yingxia | |
dc.contributor.author | Tewhey, Ryan | |
dc.contributor.author | Hatoum, Ida | |
dc.contributor.author | Shah, Naisha | |
dc.contributor.author | Lu, Yong | |
dc.contributor.author | Kristo, Fjoralba | |
dc.contributor.author | Psychogios, Nikolaos | |
dc.contributor.author | Vrbanac, Vladimir | |
dc.contributor.author | Lu, Yi-Chien | |
dc.contributor.author | Hla, Timothy T | |
dc.contributor.author | de Cabo, Rafael | |
dc.contributor.author | Tsang, John S | |
dc.contributor.author | Schadt, Eric | |
dc.contributor.author | Sabeti, Pardis Christine | |
dc.contributor.author | Kathiresan, Sekar | |
dc.contributor.author | Cohen, David E | |
dc.contributor.author | Whetstine, Johnathan | |
dc.contributor.author | Chung, Raymond Taeyong | |
dc.contributor.author | Fernández-Hernando, Carlos | |
dc.contributor.author | Kaplan, Lee Michael | |
dc.contributor.author | Bernards, Andre | |
dc.contributor.author | Gerszten, Robert Edgardo | |
dc.contributor.author | Naar, Anders Michael | |
dc.date.accessioned | 2017-03-06T17:33:03Z | |
dc.date.issued | 2015 | |
dc.identifier.citation | Wagschal, Alexandre, S Hani Najafi-Shoushtari, Lifeng Wang, Leigh Goedeke, Sumita Sinha, Andrew S deLemos, Josh C Black, et al. 2015. Genome-Wide Identification of microRNAs Regulating Cholesterol and Triglyceride Homeostasis. Nature Medicine 21, no. 11: 1290–1297. doi:10.1038/nm.3980. | en_US |
dc.identifier.issn | 1078-8956 | en_US |
dc.identifier.uri | http://nrs.harvard.edu/urn-3:HUL.InstRepos:30510306 | |
dc.description.abstract | Genome-wide association studies (GWASs) have linked genes to various pathological traits. However, the potential contribution of regulatory noncoding RNAs, such as microRNAs (miRNAs), to a genetic predisposition to pathological conditions has remained unclear. We leveraged GWAS meta-analysis data from >188,000 individuals to identify 69 miRNAs in physical proximity to single-nucleotide polymorphisms (SNPs) associated with abnormal levels of circulating lipids. Several of these miRNAs (miR-128-1, miR-148a, miR-130b, and miR-301b) control the expression of key proteins involved in cholesterol-lipoprotein trafficking, such as the low-density lipoprotein (LDL) receptor (LDLR) and the ATP-binding cassette A1 (ABCA1) cholesterol transporter. Consistent with human liver expression data and genetic links to abnormal blood lipid levels, overexpression and antisense targeting of miR-128-1 or miR-148a in high-fat diet–fed C57BL/6J and Apoe-null mice resulted in altered hepatic expression of proteins involved in lipid trafficking and metabolism, and in modulated levels of circulating lipoprotein-cholesterol and triglycerides. Taken together, these findings support the notion that altered expression of miRNAs may contribute to abnormal blood lipid levels, predisposing individuals to human cardiometabolic disorders. | en_US |
dc.description.sponsorship | Organismic and Evolutionary Biology | en_US |
dc.language.iso | en_US | en_US |
dc.publisher | Springer Nature | en_US |
dc.relation.isversionof | doi:10.1038/nm.3980 | en_US |
dc.relation.hasversion | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4993048/ | en_US |
dash.license | OAP | |
dc.title | Genome-wide identification of microRNAs regulating cholesterol and triglyceride homeostasis | en_US |
dc.type | Journal Article | en_US |
dc.description.version | Accepted Manuscript | en_US |
dc.relation.journal | Nature Medicine | en_US |
dash.depositing.author | Sabeti, Pardis Christine | |
dc.date.available | 2017-03-06T17:33:03Z | |
dc.identifier.doi | 10.1038/nm.3980 | * |
dash.authorsordered | false | |
dash.contributor.affiliated | Wagschal, Alexandre | |
dash.contributor.affiliated | Li, Yingxia | |
dash.contributor.affiliated | Tewhey, Ryan | |
dash.contributor.affiliated | Hla, Timothy | |
dash.contributor.affiliated | Naar, Anders | |
dash.contributor.affiliated | Kaplan, Lee | |
dash.contributor.affiliated | Cohen, David E. | |
dash.contributor.affiliated | Chung, Raymond | |
dash.contributor.affiliated | Gerszten, Robert | |
dash.contributor.affiliated | Whetstine, Johnathan | |
dash.contributor.affiliated | Bernards, Andre | |
dash.contributor.affiliated | Kathiresan, Sekar | |
dash.contributor.affiliated | Sabeti, Pardis | |