biostudies-literatureTan MCBNIA NIH HHSNHLBI NIH HHSNHGRI NIH HHSNCI NIH HHSNIH HHSNIGMS NIH HHS105233https://www.ebi.ac.uk/biostudies/studies/S-EPMC11284564biostudies-literatureUnknown106<h4>Background</h4>Two important questions regarding the genetics of pancreatic adenocarcinoma (PDAC) are 1. Which germline genetic variants influence the incidence of this cancer; and 2. Whether PDAC causally predisposes to associated non-malignant phenotypes, such as type 2 diabetes (T2D) and venous thromboembolism (VTE).<h4>Methods</h4>In this study of 8803 patients with PDAC and 67,523 controls, we first performed a large-scale transcriptome-wide association study to investigate the association between genetically determined gene expression in normal pancreas tissue and PDAC risk. Secondly, we used Mendelian Randomization (MR) to analyse the causal relationships among PDAC, T2D (74,124 cases and 824,006 controls) and VTE (30,234 cases and 172,122 controls).<h4>Findings</h4>Sixteen geneEBioMedicineTranscriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism.PMC11284564R35 HG010718R01 HG011138U24 OD035523HHSN268201100011IK07 CA140790R56 AG068026R01 CA154823R01 GM140287Gabrielsen MPankratz NWu LGamazon ERPattee JArmasu SWang LHaessler JTaylor KHveem KGordon WMacDonald JKabrhel CMcCauley BReiner ABraekkan SSuchon PMorange PEHeit JBammler TDeleuze JFFrazer KPsaty BMcKnight BGermain MKraft PTregouet DAPuurunen MIbrahim MBrumpton BGiulianini FPankow JHeckbert SKim JHansen JBLiu YBrody JJohnson AZhou DTang WNielsen JTan MCBDe Andrade MINVENT ConsortiumIsom CAJackson RRosendaal FSmith EChasman DVan Hylckama Vlieg AO'Donnell CSmith NLindstrom SChen MHKooperberg CWiggins KTurman CRidker PfalseTranscriptome-wide association study and Mendelian randomization in pancreatic cancer identifies susceptibility genes and causal relationships with type 2 diabetes and venous thromboembolism.<h4>Background</h4>Two important questions regarding the genetics of pancreatic adenocarcinoma (PDAC) are 1. Which germline genetic variants influence the incidence of this cancer; and 2. Whether PDAC causally predisposes to associated non-malignant phenotypes, such as type 2 diabetes (T2D) and venous thromboembolism (VTE).<h4>Methods</h4>In this study of 8803 patients with PDAC and 67,523 controls, we first performed a large-scale transcriptome-wide association study to investigate the association between genetically determined gene expression in normal pancreas tissue and PDAC risk. Secondly, we used Mendelian Randomization (MR) to analyse the causal relationships among PDAC, T2D (74,124 cases and 824,006 controls) and VTE (30,234 cases and 172,122 controls).<h4>Findings</h4>Sixteen gene2024-01-01T00:00:00Z2024 Aug2026-06-01T06:51:25.453Z2025-08-27T03:10:58.961ZS-EPMC112845643900238610.1016/j.ebiom.2024.105233