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    Genome-wide association study of pancreatic fat: The Multiethnic Cohort Adiposity Phenotype Study

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    Author
    Streicher, Samantha A
    Lim, Unhee
    Park, S Lani
    Li, Yuqing
    Sheng, Xin
    Hom, Victor
    Xia, Lucy
    Pooler, Loreall
    Shepherd, John
    Loo, Lenora W M
    Darst, Burcu F
    Highland, Heather M
    Polfus, Linda M
    Bogumil, David
    Ernst, Thomas
    Buchthal, Steven
    Franke, Adrian A
    Setiawan, Veronica Wendy
    Tiirikainen, Maarit
    Wilkens, Lynne R
    Haiman, Christopher A
    Stram, Daniel O
    Cheng, Iona
    Le Marchand, Loïc
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    Date
    2021-07-30
    Journal
    PLoS ONE
    Publisher
    Public Library of Science
    Type
    Article
    
    Metadata
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    See at
    https://doi.org/10.1371/journal.pone.0249615
    Abstract
    Several studies have found associations between higher pancreatic fat content and adverse health outcomes, such as diabetes and the metabolic syndrome, but investigations into the genetic contributions to pancreatic fat are limited. This genome-wide association study, comprised of 804 participants with MRI-assessed pancreatic fat measurements, was conducted in the ethnically diverse Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS). Two genetic variants reaching genome-wide significance, rs73449607 on chromosome 13q21.2 (Beta = -0.67, P = 4.50x10-8) and rs7996760 on chromosome 6q14 (Beta = -0.90, P = 4.91x10-8) were associated with percent pancreatic fat on the log scale. Rs73449607 was most common in the African American population (13%) and rs79967607 was most common in the European American population (6%). Rs73449607 was also associated with lower risk of type 2 diabetes (OR = 0.95, 95% CI = 0.89-1.00, P = 0.047) in the Population Architecture Genomics and Epidemiology (PAGE) Study and the DIAbetes Genetics Replication and Meta-analysis (DIAGRAM), which included substantial numbers of non-European ancestry participants (53,102 cases and 193,679 controls). Rs73449607 is located in an intergenic region between GSX1 and PLUTO, and rs79967607 is in intron 1 of EPM2A. PLUTO, a lncRNA, regulates transcription of an adjacent gene, PDX1, that controls beta-cell function in the mature pancreas, and EPM2A encodes the protein laforin, which plays a critical role in regulating glycogen production. If validated, these variants may suggest a genetic component for pancreatic fat and a common etiologic link between pancreatic fat and type 2 diabetes.
    Keyword
    pancreatic fat
    Adiposity--genetics
    Genome-Wide Association Study
    Multiethnic Cohort-Adiposity Phenotype Study (MEC-APS)
    Pancreas
    Identifier to cite or link to this item
    http://hdl.handle.net/10713/16291
    ae974a485f413a2113503eed53cd6c53
    10.1371/journal.pone.0249615
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