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Genetic regulation of plasma lipid species and their association with metabolic phenotypes

Jha, Pooja
McDevitt, Molly T
Halilbasic, Emina
Williams, Evan G
Quiros, Pedro M
Sleiman, Maroun B
Gupta, Rahul
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Published in Cell Systems. 2018, vol. 6, no. 6, p. 709-721.e6
Abstract The genetic regulation and physiological impact of most lipid species are unexplored. Here, we profiled 129 plasma lipid species across 49 strains of the BXD mouse genetic reference population fed either chow or a high-fat diet. By integrating these data with genomics and phenomics datasets, we elucidated genes by environment (diet) interactions that regulate systemic metabolism. We found quantitative trait loci (QTLs) for ∼94% of the lipids measured. Several QTLs harbored genes associated with blood lipid levels and abnormal lipid metabolism in human genome-wide association studies. Lipid species from different classes provided signatures of metabolic health, including seven plasma triglyceride species that associated with either healthy or fatty liver. This observation was further validated in an independent mouse model of non-alcoholic fatty liver disease (NAFLD) and in plasma from NAFLD patients. This work provides a resource to identify plausible genes regulating the measured lipid species and their association with metabolic traits.
Keywords AdultAnimalsCohort StudiesDietHigh-FatDisease ModelsAnimalFemaleGene Expression Regulation/geneticsGenome-Wide Association StudyHumansLipid Metabolism/genetics/physiologyLipids/blood/genetics/physiologyLiver/metabolismMaleMiceMiceInbred C57BLMiceInbred DBAMiddle AgedNon-alcoholic Fatty Liver Disease/geneticsProspective StudiesQuantitative Trait LociTriglycerides/metabolism
PMID: 29909275
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Research group Laboratoire de recherche NAFLD et résistance à l'insuline (997)
Swiss National Science Foundation: 31003A_140780
(ISO format)
JHA, Pooja et al. Genetic regulation of plasma lipid species and their association with metabolic phenotypes. In: Cell Systems, 2018, vol. 6, n° 6, p. 709-721.e6. doi: 10.1016/j.cels.2018.05.009 https://archive-ouverte.unige.ch/unige:143017

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Deposited on : 2020-10-13

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