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000305735 1001_ $$aZhang, Ting$$b0
000305735 245__ $$aDifferent diabetes types and pancreatic ductal adenocarcinoma: a Mendelian randomization and pathway/gene-set analysis.
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000305735 520__ $$aThe associations between different types of diabetes, characterized by distinct pathophysiology and genetic architecture, and pancreatic ductal adenocarcinoma (PDAC) risk are not understood.We investigated associations of genetic susceptibility to type 2 diabetes (T2D), eight T2D mechanistic clusters, type 1 diabetes (T1D), and maturity-onset diabetes of the young (MODY) with PDAC risk. We used genome-wide association study (GWAS) summary-level statistics for T2D (242,283 cases, 1,569,734 controls), T1D (18,942 cases, 501,638 controls), and PDAC (10,244 cases and 360,535 controls) in individuals of European ancestry.Two-sample Mendelian randomization (MR) using the Robust Adjusted Profile Score (MR-RAPS) method indicated that genetically predicted T2D was associated with PDAC risk (OR = 1.10; 95% CI 1.05-1.15), particularly the T2D obesity (OR = 1.28; 95% CI 1.15-1.42) and lipodystrophy (OR = 1.25; 95% CI 1.03-1.51) clusters. No association was observed for T1D with PDAC risk (OR = 1.01; 95% CI 0.99-1.02). Pathway/gene-set analysis using the summary-based Adaptive Rank Truncated Product (sARTP) method revealed a significant association between the MODY gene-sets and PDAC risk (P = 1.5 × 10-8), which remained after excluding 20 known PDAC GWAS loci (P = 7.6 × 10-4). HNF1A, FOXA3, and HNF4A were the top contributing genes after excluding the previously identified GWAS loci regions.Our results from this genetic association study support that T2D, particularly the obesity and lipodystrophy mechanistic clusters, and MODY genomic susceptibility regions play a role in the etiology of PDAC.
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000305735 650_7 $$2Other$$aMaturity-onset diabetes of the young
000305735 650_7 $$2Other$$aMendelian Randomization
000305735 650_7 $$2Other$$aPancreatic ductal adenocarcinoma
000305735 650_7 $$2Other$$aType 1 Diabetes
000305735 650_7 $$2Other$$aType 2 Diabetes
000305735 7001_ $$aHua, Xing$$b1
000305735 7001_ $$aMohindroo, Chirayu$$b2
000305735 7001_ $$aWang, Xiaoyu$$b3
000305735 7001_ $$aDutta, Diptavo$$b4
000305735 7001_ $$aLiu, Jia$$b5
000305735 7001_ $$aKatta, Shilpa$$b6
000305735 7001_ $$aLi, Shengchao A$$b7
000305735 7001_ $$aWang, Jiahui$$b8
000305735 7001_ $$aAntwi, Samuel O$$b9
000305735 7001_ $$aArslan, Alan A$$b10
000305735 7001_ $$aBeane Freeman, Laura E$$b11
000305735 7001_ $$aBracci, Paige M$$b12
000305735 7001_ $$0P:(DE-He78)5323704270b6393dcea70186ffd86bca$$aCanzian, Federico$$b13$$udkfz
000305735 7001_ $$aDu, Mengmeng$$b14
000305735 7001_ $$aGallinger, Steven$$b15
000305735 7001_ $$aGoodman, Phyllis J$$b16
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000305735 7001_ $$aKooperberg, Charles$$b18
000305735 7001_ $$aLe Marchand, Loic$$b19
000305735 7001_ $$aNeale, Rachel E$$b20
000305735 7001_ $$aPatel, Alpa V$$b21
000305735 7001_ $$aPerdomo, Sandra$$b22
000305735 7001_ $$aShu, Xiao-Ou$$b23
000305735 7001_ $$aVisvanathan, Kala$$b24
000305735 7001_ $$aVan Den Eeden, Stephen K$$b25
000305735 7001_ $$aWhite, Emily$$b26
000305735 7001_ $$aZheng, Wei$$b27
000305735 7001_ $$aAlbanes, Demetrius$$b28
000305735 7001_ $$aAndreotti, Gabriella$$b29
000305735 7001_ $$aBamlet, William R$$b30
000305735 7001_ $$aBrennan, Paul$$b31
000305735 7001_ $$aBuring, Julie E$$b32
000305735 7001_ $$aChanock, Stephen J$$b33
000305735 7001_ $$aChen, Yu$$b34
000305735 7001_ $$aDarst, Burcu$$b35
000305735 7001_ $$aFerrari, Pietro$$b36
000305735 7001_ $$aGiovannucci, Edward L$$b37
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000305735 7001_ $$aHaiman, Christopher$$b39
000305735 7001_ $$aHassan, Manal$$b40
000305735 7001_ $$aHolly, Elizabeth A$$b41
000305735 7001_ $$aHung, Rayjean J$$b42
000305735 7001_ $$aJones, Miranda R$$b43
000305735 7001_ $$aKraft, Peter$$b44
000305735 7001_ $$aKurtz, Robert C$$b45
000305735 7001_ $$aMalats, Núria$$b46
000305735 7001_ $$aMoore, Steven C$$b47
000305735 7001_ $$aNg, Kimmie$$b48
000305735 7001_ $$aOberg, Ann L$$b49
000305735 7001_ $$aOrlow, Irene$$b50
000305735 7001_ $$aPeters, Ulrike$$b51
000305735 7001_ $$aPorta, Miquel$$b52
000305735 7001_ $$aRabe, Kari G$$b53
000305735 7001_ $$aRothman, Nathaniel$$b54
000305735 7001_ $$aSánchez, Maria-José$$b55
000305735 7001_ $$aSesso, Howard D$$b56
000305735 7001_ $$aSilverman, Debra T$$b57
000305735 7001_ $$aSouthey, Melissa C$$b58
000305735 7001_ $$aUm, Caroline Y$$b59
000305735 7001_ $$aYarmolinsky, James$$b60
000305735 7001_ $$aYu, Herbert$$b61
000305735 7001_ $$aYuan, Chen$$b62
000305735 7001_ $$aZhong, Jun$$b63
000305735 7001_ $$aWolpin, Brian M$$b64
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000305735 7001_ $$aKlein, Alison P$$b67
000305735 7001_ $$aYu, Kai$$b68
000305735 7001_ $$aZhang, Haoyu$$b69
000305735 7001_ $$aStolzenberg-Solomon, Rachael Z$$b70
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