Genome-wide association study of pancreatic fat: The Multiethnic Cohort Adiposity Phenotype Study
Author
Streicher, Samantha ALim, 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
Date
2021-07-30Journal
PLoS ONEPublisher
Public Library of ScienceType
Article
Metadata
Show full item recordAbstract
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 fatAdiposity--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/10713/16291ae974a485f413a2113503eed53cd6c53
10.1371/journal.pone.0249615
Scopus Count
Collections
Related articles
- Genome-wide association study of abdominal MRI-measured visceral fat: The multiethnic cohort adiposity phenotype study.
- Authors: Streicher SA, Lim U, Park SL, Li Y, Sheng X, Hom V, Xia L, Pooler L, Shepherd J, Loo LWM, Ernst T, Buchthal S, Franke AA, Tiirikainen M, Wilkens LR, Haiman CA, Stram DO, Cheng I, Le Marchand L
- Issue date: 2023
- Susceptibility variants for waist size in relation to abdominal, visceral, and hepatic adiposity in postmenopausal women.
- Authors: Lim U, Ernst T, Wilkens LR, Albright CL, Lum-Jones A, Seifried A, Buchthal SD, Novotny R, Kolonel LN, Chang L, Cheng I, Le Marchand L
- Issue date: 2012 Jul
- Generalization and fine mapping of European ancestry-based central adiposity variants in African ancestry populations.
- Authors: Yoneyama S, Yao J, Guo X, Fernandez-Rhodes L, Lim U, Boston J, Buzková P, Carlson CS, Cheng I, Cochran B, Cooper R, Ehret G, Fornage M, Gong J, Gross M, Gu CC, Haessler J, Haiman CA, Henderson B, Hindorff LA, Houston D, Irvin MR, Jackson R, Kuller L, Leppert M, Lewis CE, Li R, Le Marchand L, Matise TC, Nguyen KD, Chakravarti A, Pankow JS, Pankratz N, Pooler L, Ritchie MD, Bien SA, Wassel CL, Chen YI, Taylor KD, Allison M, Rotter JI, Schreiner PJ, Schumacher F, Wilkens L, Boerwinkle E, Kooperberg C, Peters U, Buyske S, Graff M, North KE
- Issue date: 2017 Feb
- Pancreatic Steatosis Associates With Impaired Insulin Secretion in Genetically Predisposed Individuals.
- Authors: Wagner R, Jaghutriz BA, Gerst F, Barroso Oquendo M, Machann J, Schick F, Löffler MW, Nadalin S, Fend F, Königsrainer A, Peter A, Siegel-Axel D, Ullrich S, Häring HU, Fritsche A, Heni M
- Issue date: 2020 Nov 1
- Association of Genetic Variants Related to Gluteofemoral vs Abdominal Fat Distribution With Type 2 Diabetes, Coronary Disease, and Cardiovascular Risk Factors.
- Authors: Lotta LA, Wittemans LBL, Zuber V, Stewart ID, Sharp SJ, Luan J, Day FR, Li C, Bowker N, Cai L, De Lucia Rolfe E, Khaw KT, Perry JRB, O'Rahilly S, Scott RA, Savage DB, Burgess S, Wareham NJ, Langenberg C
- Issue date: 2018 Dec 25