This study shows EPA induces an anti-inflammatory transcriptomic profile in CD4+ T cells, independent of triglyceride lowering, potentially explaining its cardiovascular benefits.

bioRxiv · Mar 15, 2024 · PreprintGenomics

Oleic acid triggers CD4+ T cells to be metabolically rewired and poised to differentiate into proinflammatory T cell subsets upon activation

Nathalie A. Reilly, Friederike Sonnet, Koen F. Dekkers, Joanneke C. Kwekkeboom, Lucy Sinke, Stan T. Hilt, Hayat M. Suleiman, Marten A. Hoeksema, Hailiang Mei, Erik W. van Zwet, Bart Everts, Andreea Ioan‐Facsinay, J. Wouter Jukema, Bastiaan T. Heijmans

This study shows that oleic acid pre-exposure rewires CD4+ T cell metabolism, promoting pro-inflammatory differentiation upon activation.

bioRxiv · Feb 16, 2024 · PreprintGenomics

Genetic analysis of blood molecular phenotypes reveals regulatory networks affecting complex traits: a DIRECT study.

Andrew Anand Brown, Juan J. Fernandez-Tajes, Mun‐Gwan Hong, Caroline Brorsson, Robert Wilhelm Koivula, David Davtian, Théo Dupuis, Ambra Sartori, Theodora-Dafni Michalettou, Ian M. Forgie, Jonathan Adam, Kristine Højgaard Allin, Robert J. Caiazzo, Henna Cederberg, Federico De Masi, , Ulrik Plesner Jacobsen

The paper identifies shared genetic regulation across mRNA, proteins, and metabolites in blood, revealing networks and mediators of GWAS variants.

Nature Communications · Aug 21, 2023Peer-reviewedGenetic & Genomic Medicine

Pharmacogenomics of GLP-1 Receptor Agonists: A genome-wide analysis of observational data and large randomized controlled trials

Adem Y. Dawed, Andrea Mari, Andrew Anand Brown, Timothy James McDonald, Lin Li, Shuaicheng Wang, Mun‐Gwan Hong, Sapna Sharma, Neil R. Robertson, Anubha Mahajan, Xuan Wang, Mark Walker, Stephen Charles Langford Gough, Leen M. ‘t Hart, Kaixin Zhou, , A. Jonsson

This study identifies genetic variants associated with glycaemic response to GLP-1 receptor agonists using observational and trial data, finding variants in GLP-1R and ARRB1 linked to HbA1c reduction.

The Lancet Diabetes & Endocrinology · Dec 15, 2022Peer-reviewedGenetic & Genomic Medicine

Genomic and phenomic insights from an atlas of genetic effects on DNA methylation

Josine L. Min, Gibran Hemani, Eilis J. Hannon, Koen F. Dekkers, Juan Castillo Fernandez, René Luijk, Elena Carnero‐Montoro, Daniel John Lawson, Kimberley Burrows, Matthew J Suderman, Andrew D. Bretherick, Tom G. Richardson, Johanna Klughammer, Valentina Iotchkova, Gemma C. Sharp, , Marinus H. van IJzendoorn

The paper identifies genetic variants influencing DNA methylation in blood and shows their associations with complex traits and diseases, but finds limited direct causality.

Nature Genetics · Sep 1, 2021Peer-reviewedGenetic & Genomic Medicine

Sex-dependent gene regulation of human atherosclerotic plaques by DNA methylation and transcriptome integration points to smooth muscle cell involvement in women.

Robin J. G. Hartman, Marten Antoon Siemelink, Saskia Haitjema, Koen F. Dekkers, Lotte Slenders, Arjan Boltjes, Michal Mokrý, Nathalie Timmerman, Gert Jan de Borst, Bas T. Heijmans, Folkert Wouter Asselbergs, Gerard Pasterkamp, Sander W. van der Laan, Hester M. den Ruijter

Atherosclerosis · Aug 1, 2021Peer-reviewedGenomics

Genome-wide identification of genes regulating DNA methylation using genetic anchors for causal inference

Paul J. Hop, René Luijk, Lucia Daxinger, Maarten van Iterson, Koen F. Dekkers, Rick Jansen, Bastiaan T. Heijmans, Peter A.C. ’t Hoen, Joyce B. J. van Meurs, Lude Franke, Dorret Irene Boomsma, René Pool, Jenny van Dongen, Jouke‐Jan Hottenga, Marleen M. J. van Greevenbroek, , M. Arfan Ikram

The paper identifies 818 genes influencing DNA methylation in blood using genetic anchors and causal inference, revealing both transcription factors and non-DNA-binding proteins with regulatory roles.

Genome biology · Aug 28, 2020Peer-reviewedGenomics

Variation in the plasma membrane monoamine transporter (PMAT, encoded in SLC29A4) and organic cation transporter 1 (OCT1, encoded in SLC22A1) and gastrointestinal intolerance to metformin in type 2 diabetes: an IMI DIRECT study

Adem Y. Dawed, Kaixin Zhou, Nienke van Leeuwen, Anubha Mahajan, Neil Robertson, Robert Wilhelm Koivula, Petra J. M. Elders, Simone P. Rauh, Angus G. Jones, Reinhard Walter Holl, Julia Stingl, Paul W. Franks, Mark I. McCarthy, Leen M. ‘t Hart, Ewan R. Pearson, , A. Forman

This study investigates the association between genetic variants in PMAT and OCT1 transporters and metformin gastrointestinal intolerance in type 2 diabetes patients.

Diabetes Care · Mar 18, 2019Peer-reviewedGenetics

Genome-wide identification of directed gene networks using large-scale population genomics data

René Luijk, Koen F. Dekkers, Maarten van Iterson, Wibowo Arindrarto, Annique Claringbould, Paul J. Hop, Dorret Irene Boomsma, Cornelia M. van Duijn, Marleen M. J. van Greevenbroek, Jan Herman Veldink, Cisca Wijmenga, Lude Franke, Peter A.C. ’t Hoen, Rick Jansen, Joyce B. J. van Meurs, , Diana van Heemst

The paper identifies 49 gene drivers of downstream transcriptional changes using population genomics data and RNA-sequencing from 3,072 individuals.

Nature Communications · Jul 31, 2018Peer-reviewedGenomics