Farnir, Frédéric ; Université de Liège - ULiège > Fundamental and Applied Research for Animals and Health (FARAH) > FARAH: Productions animales durables
Vieujean, Sophie
Regimont, Sarah ; Université de Liège - ULiège > Département des sciences biomédicales et précliniques
Mni, Myriam ; Université de Liège - ULiège > GIGA > GIGA Molecular & Computational Biology - Unit of Animal Genomics
WERY, Marie ; Centre Hospitalier Universitaire de Liège - CHU > > Service de neurologie
Azarzar, Samira ; Université de Liège - ULiège > GIGA > GIGA Molecular & Computational Biology - Unit of Animal Genomics
Busse, R. et al. Tackling chronic disease in Europe: strategies, interventions and challenges. in European Observatory on Health Systems and Policies. Observatory Studies Series n°20 (World Health Organization, 2010).
Schumacher A Gassmann O Hinder M Changing R&D models in research-based pharmaceutical companies J. Transl. Med 2016 14 10.1186/s12967-016-0838-4 105
Jakab, M. et al. Health systems respond to noncommunicable diseases: time for ambition. Copenhagen: WHO Regional Office for Europe. https://www.who.int/europe/publications/i/item/9789289053402 (2018).
Polubriaginof FCG et al. Disease heritability inferred from familial relationships reported in medical records Cell 2018 173 1692 1704 1:CAS:528:DC%2BC1cXpvVemsrg%3D 29779949 6015747 10.1016/j.cell.2018.04.032
Visscher PM et al. 10 Years of GWAS discovery: biology, function, and translation Am. J. Hum. Genet. 2017 101 5 22 1:CAS:528:DC%2BC2sXhtFChu7rI 28686856 5501872 10.1016/j.ajhg.2017.06.005
Abdelloui A Yengo L Verweij KJH Visscher PM 15 years of GWAS discovery: realizing the promise Am. J. Hum. Genet. 2023 110 179 194 10.1016/j.ajhg.2022.12.011
King EA Davis JW Degner JF Are drug targets with genetic support twice as likely to be approved? Revised estimates of the impact of genetic support for drug mechanisms on the probability of drug approval PLoS Genet. 2019 15 e1008489 31830040 6907751 10.1371/journal.pgen.1008489
Burgess S et al. Using genetic association data to guide drug discovery and development: review of methods and applications Am. J. Hum. Genet. 2023 110 195 214 1:CAS:528:DC%2BB3sXisFartr4%3D 36736292 9943784 10.1016/j.ajhg.2022.12.017
Trajanoska K et al. From target discovery to clinical drug development with human genetics Nature 2023 620 737 745 2023Natur.620.737T 1:CAS:528:DC%2BB3sXhslGrsL%2FF 10.1038/s41586-023-06388-8 37612393
Minikel EV Painter JL Dong CC Nelson MR Refining the impact of genetic evidence on clinical success Nature 2024 629 624 629 2024Natur.629.624M 1:CAS:528:DC%2BB2cXoslGgtrY%3D 10.1038/s41586-024-07316-0 38632401 11096124
Sazonovs A et al. Large-scale sequencing identifies multiple genes and rare variants associated with Crohn’s disease susceptibility Nat. Genet. 2022 54 1275 1283 1:CAS:528:DC%2BB38Xit1Ojtb7M 10.1038/s41588-022-01156-2 36038634 9700438
Giambertolomei C et al. Bayesian test for colocalization between pairs of genetic association studies using summary statistics PLoS Genet. 2014 10 e1004383 10.1371/journal.pgen.1004383
Zhu Z et al. Integration of summary data from GWAS and eQTL studies predicts complex trait gene targets Nat. Genet. 2016 48 481 487 1:CAS:528:DC%2BC28XkvFGrs7g%3D 10.1038/ng.3538 27019110
Hormozdiari F et al. Colocalization of GWAS and eQTL signals detects target genes Am. J. Hum. Genet. 2016 99 1245 1260 1:CAS:528:DC%2BC28XhvFSitLfJ 27866706 5142122 10.1016/j.ajhg.2016.10.003
Momozawa Y et al. IBD risk loci are enriched in multigenic regulatory modules encompassing putative causative genes Nat. Commun. 2018 9 2018NatCo..9.2427M 10.1038/s41467-018-04365-8 29930244 6013502 2427
GTEx Consortium. The GTEx Consortium atlas of genetic regulatory effects across human tissues. Science369, 1318–1330 (2020).
Umans BD Battle A Gilad Y Where are the disease-associated eQTLs? Trends Genet. 2021 37 109 124 1:CAS:528:DC%2BB3cXhslWqt7%2FL 32912663 10.1016/j.tig.2020.08.009
Mostafavi H Spence JP Naqvi S Pritchard JK Systematic differences in discovery of genetic effects on gene expression and complex traits Nat. Genet 2023 55 1866 1875 1:CAS:528:DC%2BB3sXitFOqsL%2FN 10.1038/s41588-023-01529-1 37857933 12270542
Delaneau O et al. A complete tool set for molecular QTL discovery and analysis Nat. Commun. 2017 8 2017NatCo..815452D 1:CAS:528:DC%2BC2sXotFyisrk%3D 10.1038/ncomms15452 28516912 5454369 15452
Storey JD Tibshirani R Statistical significance for genomewide studies Proc. Natl. Acad. Sci. USA 2003 100 9440 9445 2003PNAS.100.9440S 1994856 1:CAS:528:DC%2BD3sXmtlyktbY%3D 12883005 170937 10.1073/pnas.1530509100
Korsunsky I et al. Raychaudhuri S. Fast, sensitive and accurate integration of single-cell data with Harmony Nat. Methods 2019 16 1289 1296 1:CAS:528:DC%2BC1MXitFOqsr7N 10.1038/s41592-019-0619-0 31740819 6884693
Smillie CS et al. Intra- and Inter-cellular Rewiring of the Human Colon during Ulcerative Colitis Cell 2019 178 714 730.e22 1:CAS:528:DC%2BC1MXhsVOgsL7K 31348891 6662628 10.1016/j.cell.2019.06.029
Franzén, O., Gan, L.-M., & Björkegren, J. L. M. PanglaoDB: a web server for exploration of mouse and human single-cell RNA sequencing data. Database 2019: baz046 https://doi.org/10.1093/database/baz046 (2019).
Hao Y et al. Integrated analysis of multimodal single-cell data Cell 2021 184 3573 3587.e29 1:CAS:528:DC%2BB3MXhtlSrtrvE 34062119 8238499 10.1016/j.cell.2021.04.048
Burclaff J et al. A proximal-to-distal survey of healthy adult human small intestine and colon epithelium by single-cell transcriptomics Cell Mol. Gastroenterol. Hepatol. 2022 13 1554 1589 1:CAS:528:DC%2BB38Xntlyns7c%3D 35176508 9043569 10.1016/j.jcmgh.2022.02.007
Ishikawa K et al. Identification of quiescent LGR5+ stem cells in the human colon Gastroenterology 2022 163 1391 1406 1:CAS:528:DC%2BB38XislCms7%2FF 35963362 10.1053/j.gastro.2022.07.081
Hickey JW et al. Organization of the human intestine at single-cell resolution Nature 2023 619 572 584 2023Natur.619.572H 1:CAS:528:DC%2BB3sXhsFSmtLnK 10.1038/s41586-023-05915-x 37468586 10356619
Kong L et al. The landscape of immune dysregulation in Crohn’s disease revealed through single-cell transcriptomic profiling in the ileum and colon Immunity 2023 56 444 458.e5 1:CAS:528:DC%2BB3sXitFOiu7o%3D 36720220 9957882 10.1016/j.immuni.2023.01.002
Krzak, M. et al. Single-cell RNA sequencing of terminalileal biopsies identifi es signatures of Crohn's disease pathogenesis. Nat Genet.58, 1610–1619 (2026).
Stegle O Parts L Durbin R Winn J A Bayesian framework to account for complex non-genetic factors in gene expression levels greatly increases power in eQTL studies PLoS Comput. Biol. 2010 6 e1000770 2010PLSCB..6E0770S 2659818 20463871 2865505 10.1371/journal.pcbi.1000770
van de Geijn B McVicker G Gilad Y Pritchard JK WASP: allele-specific software for robust molecular quantitative trait locus discovery Nat. Methods 2016 12 1061 1063 10.1038/nmeth.3582
de Lange K et al. Genome-wide association study implicates immune activation of multiple integrin genes in inflammatory bowel disease Nat. Genet. 2017 49 256 261 10.1038/ng.3760 28067908 5289481
Jurgens SJ et al. Genome-wide association study reveals mechanisms underlying dilated cardiomyopathy and myocardial resilience Nat. Genet. 2024 56 2636 2645 1:CAS:528:DC%2BB2cXisFOlurfI 10.1038/s41588-024-01975-5 39572784 11631763
Yıldız Ç et al. A possibly new autoinflammatory disease due to compound heterozygous phosphomevalonate kinase gene mutation Jt. Bone Spine 2023 90 105490 10.1016/j.jbspin.2022.105490
Zou D Zhou S Wang H Gou J Wang S Knee joint swelling at presentation: a case of pediatric Crohn disease with a TNFAIP3 mutation Pediatrics 2020 146 e20193416 33177168 10.1542/peds.2019-3416
Taniguchi K et al. Novel TNFAIP3 microdeletion in a girl with infantile-onset inflammatory bowel disease complicated by a severe perianal lesion Hum. Genome Var. 2021 8 1 1:CAS:528:DC%2BB3MXmtFSlt78%3D 10.1038/s41439-020-00128-4 33446651 7809258
Roncagalli R et al. The scaffolding function of the RLTPR protein explains its essential role for CD28 co-stimulation in mouse and human T cells J. Exp. Med. 2016 213 2437 2457 1:CAS:528:DC%2BC2sXhsVygurc%3D 27647348 5068240 10.1084/jem.20160579
Magg T et al. CARMIL2 deficiency presenting as very early onset inflammatory bowel disease Inflamm. Bowel Dis. 2019 25 1788 1795 31115454 6799948 10.1093/ibd/izz103
Bosa L et al. Novel CARMIL2 loss-of-function variants are associated with pediatric inflammatory bowel disease Sci. Rep. 2021 11 2021NatSR.11.5945B 1:CAS:528:DC%2BB3MXmslKgtLs%3D 10.1038/s41598-021-85399-9 33723309 7960730 5945
Liu F et al. TLR-induced SMPD3 defects enhance inflammatory response of B cell and macrophage in the pathogenesis of SLE Scand. J. Immunol. 2017 86 377 388 1:CAS:528:DC%2BC2sXhs1Cms7jJ 28889482 10.1111/sji.12611
Al-Rashed F et al. Neutral sphingomyelinase 2 regulates inflammatory responses in monocytes/macrophages induced by TNF-α Sci. Rep. 2020 10 2020NatSR.1016802A 1:CAS:528:DC%2BB3cXitVGgt7%2FJ 10.1038/s41598-020-73912-5 33033337 7544688 16802
Li, S. et al. Sedanolide alleviates DSS-induced colitis by modulating the intestinal FXR-SMPD3 pathway in mice. J. Adv. Reshttps://doi.org/10.1016/j.jare.2024.03.026 (2024).
Yu, M. et al. International inflammatory bowel disease genetics consortium sequencing group; Lamb CA, Anderson CA, Daly MJ, Huang H. Cystic fibrosis risk variants confer protection against inflammatory bowel disease. Cell Genom.6, 101071 (2026).
Hallows KR Kobinger GP Wilson JM Witters LA Foskett JK Physiological modulation of CFTR activity by AMP-activated protein kinase in polarized T84 cells Am. J. Physiol. Cell Physiol. 2003 284 C1297 C1308 1:CAS:528:DC%2BD3sXjvFGqt7g%3D 12519745 10.1152/ajpcell.00227.2002
Prieto S et al. CDK8 and CDK19 act redundantly to control the CFTR pathway in the intestinal epithelium EMBO Rep. 2022 24 e54261 10.15252/embr.202154261 36545778 10549226
Belinky F et al. PathCards: multi-source consolidation of human biological pathways Database 2015 2015 bav006 25725062 4343183 10.1093/database/bav006
Dimitrov G et al. Congenital Sodium Diarrhea by mutation of the SLC9A3 gene Eur. J. Med. Genet. 2019 262 103712 10.1016/j.ejmg.2019.103712
Eldjarn GH et al. Large-scale plasma proteomics comparisons through genetics and disease associations Nature 2023 622 348 358 2023Natur.622.348E 1:CAS:528:DC%2BB3sXitVGqsbvP 10.1038/s41586-023-06563-x 37794188 10567571
Mountjoy E et al. An open approach to systematically prioritize causal variants and genes at all published human GWAS trait-associated loci Nat. Genet. 2021 53 1527 1533 1:CAS:528:DC%2BB3MXitlOlurbE 10.1038/s41588-021-00945-5 34711957 7611956
Vieujean, S. et al. Understanding the therapeutic toolkit for inflammatory bowel disease. Nat. Rev. Gastroenterol. Hepatol. 22, 371–394 (2024).
Liu D Offin M Harnicar S Li BT Drilon A Entrectinib: an orally available, selective tyrosine kinase inhibitor for the treatment of NTRK, ROS1, and ALK fusion-positive solid tumors Ther. Clin. Risk Manag 2018 14 1247 1252 1:CAS:528:DC%2BC1MXhs1Ontr3K 30050303 6055893 10.2147/TCRM.S147381
Jin X et al. Entrectinib inhibits NLRP3 inflammasome and inflammatory diseases by directly targeting NEK7 Cell Rep. Med. 2023 4 101310 1:CAS:528:DC%2BB2cXhtlalsw%3D%3D 38118409 10772347 10.1016/j.xcrm.2023.101310
Chen X et al. NEK7 interacts with NLRP3 to modulate the pyroptosis in inflammatory bowel disease via NF-κB signaling Cell Death Dis. 2019 10 1:CAS:528:DC%2BC1MXitlWqu7fF 10.1038/s41419-019-2157-1 31787755 6885517 906
Jiang Q Li M Li H Chen L Entrectinib, a new multi-target inhibitor for cancer therapy Biomed. Pharmacother. 2022 150 112974 1:CAS:528:DC%2BB38Xht1OmsrnI 35447552 10.1016/j.biopha.2022.112974
Schmiedel BJ et al. Impact of genetic polymorphisms on human immune cell gene expression Cell 2018 175 1701 1715 1:CAS:528:DC%2BC1cXit1Wlt77N 30449622 6289654 10.1016/j.cell.2018.10.022
Ota M et al. Dynamic landscape of immune cell-specific gene regulation in immune-mediated diseases Cell 2021 184 3006 3021.e17 1:CAS:528:DC%2BB3MXhtVSqtrvO 33930287 10.1016/j.cell.2021.03.056
Maecker HT McCoy JP Nussenblatt R Standardizing immunophenotyping for the Human Immunology Project Nat. Rev. Immunol. 2012 12 191 200 1:CAS:528:DC%2BC38XitlKnsLc%3D 10.1038/nri3158 22343568 3409649
Võsa U et al. Large-scale cis- and trans-eQTL analyses identify thousands of genetic loci and polygenic scores that regulate blood gene expression Nat. Genet 2021 53 1300 1310 10.1038/s41588-021-00913-z 34475573 8432599
Hu S et al. Inflammation status modulates the effect of host genetic variation on intestinal gene expression in inflammatory bowel disease Nat. Commun. 2021 12 2021NatCo.12.1122H 1:CAS:528:DC%2BB3MXkvFCrsro%3D 10.1038/s41467-021-21458-z 33602935 7892863 1122
Liefferinckx C et al. The identification of blood-derived response eQTL reveals complex effects of regulatory variants on inflammatory and infectious disease risk PLoS Genet. 2025 21 e1011599 1:CAS:528:DC%2BB2MXpvVWmsbs%3D 40208878 12013874 10.1371/journal.pgen.1011599
Nishiyama NC et al. eQTL in diseased colon tissue identifies potential target genes associated with IBD Nat. Commun. 2026 17 2026NatCo.17.2736N 1:CAS:528:DC%2BB28XnvVSqsbs%3D 10.1038/s41467-026-69364-6 41688467 13013683 2736
Alegbe T et al. Cell-type-resolved genetic variation shapes inflammatory bowel disease risk Nature 2026 10.1038/s41586-026-10627-z 42236949 13441992
Connally NJ et al. The missing link between genetic association and regulatory function eLife 2022 11 e74970 1:CAS:528:DC%2BB3sXisVKkt7zL 36515579 9842386 10.7554/eLife.74970
Steinmetz L et al. Dissecting the architecture of a quantitative trait locus in yeast Nature 2002 416 326 330 2002Natur.416.326S 1:CAS:528:DC%2BD38XisFSlsLg%3D 10.1038/416326a 11907579
Stern DL Identification of loci that cause phenotypic variation in diverse species with the reciprocal hemizygosity test Trends Genet. 2014 30 547 554 1:CAS:528:DC%2BC2cXhsFyqsrzI 25278102 10.1016/j.tig.2014.09.006
Hugot JP et al. Association of NOD2 leucine-rich repeat variants with susceptibility to Crohn’s disease Nature 2001 411 599 603 2001Natur.411.599H 1:CAS:528:DC%2BD3MXksVShtLY%3D 10.1038/35079107 11385576
Lesage S et al. CARD15/NOD2 mutational analysis and genotype-phenotype correlation in 612 patients with inflammatory bowel disease Am. J. Hum. Genet. 2002 70 845 857 1:CAS:528:DC%2BD38XivFClurw%3D 11875755 379113 10.1086/339432
Flannick J et al. Exome sequencing of 20,791 cases of type 2 diabetes and 24,440 controls Nature 2019 570 71 76 2019Natur.570..71F 1:CAS:528:DC%2BC1MXhtVajsrjO 10.1038/s41586-019-1231-2 31118516 6699738
Visscher PM Haley CS Detection of putative quantitative trait loci in line crosses under infinitesimal genetic models Theor. Appl. Genet. 1996 93 691 702 1:STN:280:DC%2BC2c7gt1Wkuw%3D%3D 10.1007/BF00224064 24162396
Yan J Hedl M Abraham C An inflammatory bowel disease-risk variant in INAVA decreases pattern recognition receptor-induced outcomes J. Clin. Investig. 2017 127 2192 2205 28436939 5451247 10.1172/JCI86282
Mohanan V et al. C1orf106 is a colitis risk gene that regulates stability of epithelial adherens junctions Science 2018 359 1161 1166 2018Sci..359.1161M 1:CAS:528:DC%2BC1cXjvFGrsbc%3D 29420262 6008784 10.1126/science.aan0814
Hamaoui D Subtil A ATG16L1 functions in cell homeostasis beyond autophagy FEBS J. 2022 289 1779 1800 1:CAS:528:DC%2BB3MXotFKisb0%3D 33752267 10.1111/febs.15833
Boyle EA Li YI Pritchard JK An expanded view of complex traits: from polygenic to omnigenic Cell 2017 169 1177 1186 1:CAS:528:DC%2BC2sXhtVWrtrjM 28622505 5536862 10.1016/j.cell.2017.05.038
Liu X Li YI Pritchard JK Trans effects on gene expression can drive omnigenic in heritance Cell 2019 177 1022 1034 2019Cell.177.1022L 1:CAS:528:DC%2BC1MXovVOlurs%3D 31051098 6553491 10.1016/j.cell.2019.04.014
Graham DB Xavier RJ Pathway paradigms revealed from the genetics of inflammatory bowel disease Nature 2020 578 527 539 2020Natur.578.527G 1:CAS:528:DC%2BB3cXksVyqsbg%3D 10.1038/s41586-020-2025-2 32103191 7871366
Sylvain A et al. A cereblon-based glue degrader of NEK7 regulates NLRP3 inflammasome in a context-dependent manner Cell Chem. Biol. 2025 32 955 968.e13 1:CAS:528:DC%2BB2MXhsFKlsL3N 40639372 10.1016/j.chembiol.2025.06.005
Ongen H Buil A Anand Brown A Dermitzakis ET Delaneau O Fast and efficient QTL mapper for thousands of molecular phenotypes Bioinformatics 2016 32 1479 1485 1:CAS:528:DC%2BC28XhsVGnt73E 26708335 10.1093/bioinformatics/btv722
Stoeckius M et al. Cell Hashing with barcoded antibodies enables multiplexing and doublet detection for single cell genomics Genome Biol. 2018 19 1:CAS:528:DC%2BC1MXhtVKksbfJ 10.1186/s13059-018-1603-1 30567574 6300015 224
McGinnis CS et al. MULTI-seq: sample multiplexing for single-cell RNA sequencing using lipid-tagged indices Nat. Methods 2019 16 619 626 1:CAS:528:DC%2BC1MXhtFyksbjK 10.1038/s41592-019-0433-8 31209384 6837808
Galili T dendextend: an R package for visualizing, adjusting and comparing trees of hierarchical clustering Bioinformatics 2015 31 3718 3720 1:CAS:528:DC%2BC28Xht1ensr7I 26209431 4817050 10.1093/bioinformatics/btv428
Tirosh I et al. Dissecting the multicellular ecosystem of metastatic melanoma by single-cell RNA-seq Science 2016 352 189 196 2016Sci..352.189T 1:CAS:528:DC%2BC28XlsFSmurk%3D 27124452 4944528 10.1126/science.aad0501
Bates D Mächler M Bolker B Walker S “Fitting linear mixed-effects models using lme4.” J. Stat. Softw. 2015 67 1 48 10.18637/jss.v067.i01
Kuznetsova A Brockhoff PB Christensen RHB “lmerTest package: tests in linear mixed effects models.” J. Stat. Softw. 2017 82 1 26 10.18637/jss.v082.i13
Love MI Huber W Anders S Moderated estimation of fold change and dispersion for RNA-seq data with DESeq2 Genome Biol. 2014 15 10.1186/s13059-014-0550-8 25516281 4302049 550
Zhu A Ibrahim JG Love MI Heavy-tailed prior distributions for sequence count data: removing the noise and preserving large differences Bioinformatics 2019 35 2084 2092 1:CAS:528:DC%2BB3cXhsVOltbY%3D 30395178 6581436 10.1093/bioinformatics/bty895
Finak G et al. MAST: a flexible statistical framework for assessing transcriptional changes and characterizing heterogeneity in single-cell RNA sequencing data Genome Biol. 2015 16 10.1186/s13059-015-0844-5 26653891 4676162 278
