Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study
Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study
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 = 4.50×10-8) and rs7996760 on chromosome 6q14 (Beta = ?0.90, P = 4.91×10-8) 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 suggestively 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 PLUT, and rs79967607 is in intron 1 of EPM2A. PLUT, a linkRNA, 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.
Lim Unhee、Park S. Lani、Li Yuqing、Sheng Xin、Xia Lucy、Highland Heather M、Ernst Thomas、Franke Adrian A、Setiawan Veronica Wendy、Marchand Lo?c Le、Polfus Linda M、Wilkens Lynne R、Pooler Loreall、Bogumil David、Stram Daniel O、Cheng Iona、Darst Burcu F、Tiirikainen Maarit、Buchthal Steven、Streicher Samantha A、Shepherd John、Haiman Christopher A、Hom Victor、Loo Lenora WM
University of Hawaii Cancer Center, University of Hawaii at M¨?noaUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noaDepartment of Epidemiology and Biostatistics, University of California¨CSan FranciscoCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaDepartment of Epidemiology, University of North Carolina at Chapel HillUniversity of Maryland School of MedicineUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noaCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noaCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noaCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaDepartment of Epidemiology and Biostatistics, University of California¨CSan FranciscoCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noaUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noaUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noaUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noaCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaCenter for Genetic Epidemiology, Department of Preventive Medicine, Keck School of Medicine, University of Southern CaliforniaUniversity of Hawaii Cancer Center, University of Hawaii at M¨?noa
基础医学遗传学医学研究方法
Lim Unhee,Park S. Lani,Li Yuqing,Sheng Xin,Xia Lucy,Highland Heather M,Ernst Thomas,Franke Adrian A,Setiawan Veronica Wendy,Marchand Lo?c Le,Polfus Linda M,Wilkens Lynne R,Pooler Loreall,Bogumil David,Stram Daniel O,Cheng Iona,Darst Burcu F,Tiirikainen Maarit,Buchthal Steven,Streicher Samantha A,Shepherd John,Haiman Christopher A,Hom Victor,Loo Lenora WM.Genome-wide Association Study of Pancreatic Fat: The Multiethnic Cohort Adiposity Phenotype Study[EB/OL].(2025-03-28)[2025-06-14].https://www.biorxiv.org/content/10.1101/2021.03.23.436581.点此复制
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