Multi-omics integrative analyses in type 2 diabetes and related disorders

Research scientists and clinicians involved : Toby Andrew, Amélie Bonnefond, Fabien Delahaye, Dominique Eladari, Philippe Froguel, Inga Prokopenko and Anne Vambergue


In complex polygenic forms of metabolic disorders (including putative type 2 diabetes following a gestational diabetes, NASH, putative metabolic disorders following prematurity), we perform several types of multi-omics analyses (via our EquipEx platform LIGAN) in various tissues: cord blood, placenta, whole blood, liver, skeletal muscle, pancreatic islets of Langerhans and exocrine pancreas. The multi-omics methods include DNA microarrays that are used in genome-wide association studies (GWAS), RNA next-generation sequencing (RNA-seq) possibly done in single cells (single-cell RNA-seq), methylation arrays (like Illumina EPIC arrays), next-generation sequencing of methylated loci (Methyl-seq), or even metabolomics, in order to perform integrative analyses (like eQTL, pQTL, meQTL… and MergeOmics), taking into account well-characterized phenome, enabling the identification of new pathophysiological pathways but also the optimization of patients’ stratification, towards precision medicine.




Related major publications of the team since 2015 :

– NACHO: an R package for quality control of NanoString nCounter data. Canouil M, Bouland GA, Bonnefond A, Froguel P, ‘t Hart LM, Slieker RC. Bioinformatics. 2020 Feb 1;36(3):970-971.

– The expression of genes in top obesity-associated loci is enriched in insula and substantia nigra brain regions involved in addiction and reward. Ndiaye FK, Huyvaert M, Ortalli A, Canouil M, Lecoeur C, Verbanck M, Lobbens S, Khamis A, Marselli L, Marchetti P, Kerr-Conte J, Pattou F, Marre M, Roussel R, Balkau B, Froguel P, Bonnefond A. Int J Obes (Lond). 2020 Feb;44(2):539-543.

– Laser capture microdissection of human pancreatic islets reveals novel eQTLs associated with type 2 diabetes. Khamis A, Canouil M, Siddiq A, Crouch H, Falchi M, Bulow MV, Ehehalt F, Marselli L, Distler M, Richter D, Weitz J, Bokvist K, Xenarios I, Thorens B, Schulte AM, Ibberson M, Bonnefond A, Marchetti P, Solimena M, Froguel P. Mol Metab. 2019 Jun;24:98-107.

– Epigenome-wide association study of adiposity and future risk of obesity-related diseases. Campanella G, Gunter MJ, Polidoro S, Krogh V, Palli D, Panico S, Sacerdote C, Tumino R, Fiorito G, Guarrera S, Iacoviello L, Bergdahl IA, Melin B, Lenner P, de Kok TMCM, Georgiadis P, Kleinjans JCS, Kyrtopoulos SA, Bueno-de-Mesquita HB, Lillycrop KA, May AM, Onland-Moret NC, Murray R, Riboli E, Verschuren M, Lund E, Mode N, Sandanger TM, Fiano V, Trevisan M, Matullo G, Froguel P, Elliott P, Vineis P, Chadeau-Hyam M. Int J Obes (Lond). 2018 Dec;42(12):2022-2035.

– Increased Hepatic PDGF-AA Signaling Mediates Liver Insulin Resistance in Obesity-Associated Type 2 Diabetes. Abderrahmani A, Yengo L, Caiazzo R, Canouil M, Cauchi S, Raverdy V, Plaisance V, Pawlowski V, Lobbens S, Maillet J, Rolland L, Boutry R, Queniat G, Kwapich M, Tenenbaum M, Bricambert J, Saussenthaler S, Anthony E, Jha P, Derop J, Sand O, Rabearivelo I, Leloire A, Pigeyre M, Daujat-Chavanieu M, Gerbal-Chaloin S, Dayeh T, Lassailly G, Mathurin P, Staels B, Auwerx J, Schürmann A, Postic C, Schafmayer C, Hampe J, Bonnefond A, Pattou F, Froguel P. Diabetes. 2018 Jul;67(7):1310-1321.

– Jointly Modelling Single Nucleotide Polymorphisms With Longitudinal and Time-to-Event Trait: An Application to Type 2 Diabetes and Fasting Plasma Glucose. Canouil M, Balkau B, Roussel R, Froguel P, Rocheleau G. Front Genet. 2018 Jun 14;9:210.

– Systems biology of the IMIDIA biobank from organ donors and pancreatectomised patients defines a novel transcriptomic signature of islets from individuals with type 2 diabetes. Solimena M, Schulte AM, Marselli L, Ehehalt F, Richter D, Kleeberg M, Mziaut H, Knoch KP, Parnis J, Bugliani M, Siddiq A, Jörns A, Burdet F, Liechti R, Suleiman M, Margerie D, Syed F, Distler M, Grützmann R, Petretto E, Moreno-Moral A, Wegbrod C, Sönmez A, Pfriem K, Friedrich A, Meinel J, Wollheim CB, Baretton GB, Scharfmann R, Nogoceke E, Bonifacio E, Sturm D, Meyer-Puttlitz B, Boggi U, Saeger HD, Filipponi F, Lesche M, Meda P, Dahl A, Wigger L, Xenarios I, Falchi M, Thorens B, Weitz J, Bokvist K, Lenzen S, Rutter GA, Froguel P, von Bülow M, Ibberson M, Marchetti P. Diabetologia. 2018 Mar;61(3):641-657.

– Early metabolic markers identify potential targets for the prevention of type 2 diabetes. Peddinti G, Cobb J, Yengo L, Froguel P, Kravić J, Balkau B, Tuomi T, Aittokallio T, Groop L. Diabetologia. 2017 Sep;60(9):1740-1750.

– Low-dose exposure to bisphenols A, F and S of human primary adipocyte impacts coding and non-coding RNA profiles. Verbanck M, Canouil M, Leloire A, Dhennin V, Coumoul X, Yengo L, Froguel P, Poulain-Godefroy O. PLoS One. 2017 Jun 19;12(6):e0179583

– Expression and functional assessment of candidate type 2 diabetes susceptibility genes identify four new genes contributing to human insulin secretion. Ndiaye FK, Ortalli A, Canouil M, Huyvaert M, Salazar-Cardozo C, Lecoeur C, Verbanck M, Pawlowski V, Boutry R, Durand E, Rabearivelo I, Sand O, Marselli L, Kerr-Conte J, Chandra V, Scharfmann R, Poulain-Godefroy O, Marchetti P, Pattou F, Abderrahmani A, Froguel P, Bonnefond A. Mol Metab. 2017 Apr 8;6(6):459-470.

– Relationship between salivary/pancreatic amylase and body mass index: a systems biology approach. Bonnefond A, Yengo L, Dechaume A, Canouil M, Castelain M, Roger E, Allegaert F, Caiazzo R, Raverdy V, Pigeyre M, Arredouani A, Borys JM, Lévy-Marchal C, Weill J, Roussel R, Balkau B, Marre M, Pattou F, Brousseau T, Froguel P. BMC Med. 2017 Feb 23;15(1):37.

– Decreased STARD10 Expression Is Associated with Defective Insulin Secretion in Humans and Mice. Carrat GR, Hu M, Nguyen-Tu MS, Chabosseau P, Gaulton KJ, van de Bunt M, Siddiq A, Falchi M, Thurner M, Canouil M, Pattou F, Leclerc I, Pullen TJ, Cane MC, Prabhala P, Greenwald W, Schulte A, Marchetti P, Ibberson M, MacDonald PE, Manning Fox JE, Gloyn AL, Froguel P, Solimena M, McCarthy MI, Rutter GA. Am J Hum Genet. 2017 Feb 2;100(2):238-256.

– Hepatic DPP4 DNA Methylation Associates With Fatty Liver. Baumeier C, Saussenthaler S, Kammel A, Jähnert M, Schlüter L, Hesse D, Canouil M, Lobbens S, Caiazzo R, Raverdy V, Pattou F, Nilsson E, Pihlajamäki J, Ling C, Froguel P, Schürmann A, Schwenk RW. Diabetes. 2017 Jan;66(1):25-35.

– Associations Between Type 2 Diabetes-Related Genetic Scores and Metabolic Traits, in Obese and Normal-Weight Youths. Morandi A, Bonnefond A, Lobbens S, Yengo L, Miraglia Del Giudice E, Grandone A, Lévy-Marchal C, Weill J, Maffeis C, Froguel P. J Clin Endocrinol Metab. 2016 Nov;101(11):4244-4250.

– Impact of statistical models on the prediction of type 2 diabetes using non-targeted metabolomics profiling. Yengo L, Arredouani A, Marre M, Roussel R, Vaxillaire M, Falchi M, Haoudi A, Tichet J; D.E.S.I.R Study Group, Balkau B, Bonnefond A, Froguel P. Mol Metab. 2016 Aug 23;5(10):918-925.

– Post-Bariatric Surgery Changes in Quinolinic and Xanthurenic Acid Concentrations Are Associated with Glucose Homeostasis. Favennec M, Hennart B, Verbanck M, Pigeyre M, Caiazzo R, Raverdy V, Verkindt H, Leloire A, Guillemin GJ, Yengo L, Allorge D, Froguel P, Pattou F, Poulain-Godefroy O. PLoS One. 2016 Jun 21;11(6):e0158051.

– Epigenome-wide association of DNA methylation markers in peripheral blood from Indian Asians and Europeans with incident type 2 diabetes: a nested case-control study. Chambers JC, Loh M, Lehne B, Drong A, Kriebel J, Motta V, Wahl S, Elliott HR, Rota F, Scott WR, Zhang W, Tan ST, Campanella G, Chadeau-Hyam M, Yengo L, Richmond RC, Adamowicz-Brice M, Afzal U, Bozaoglu K, Mok ZY, Ng HK, Pattou F, Prokisch H, Rozario MA, Tarantini L, Abbott J, Ala-Korpela M, Albetti B, Ammerpohl O, Bertazzi PA, Blancher C, Caiazzo R, Danesh J, Gaunt TR, de Lusignan S, Gieger C, Illig T, Jha S, Jones S, Jowett J, Kangas AJ, Kasturiratne A, Kato N, Kotea N, Kowlessur S, Pitkäniemi J, Punjabi P, Saleheen D, Schafmayer C, Soininen P, Tai ES, Thorand B, Tuomilehto J, Wickremasinghe AR, Kyrtopoulos SA, Aitman TJ, Herder C, Hampe J, Cauchi S, Relton CL, Froguel P, Soong R, Vineis P, Jarvelin MR, Scott J, Grallert H, Bollati V, Elliott P, McCarthy MI, Kooner JS. Lancet Diabetes Endocrinol. 2015 Jul;3(7):526-534.

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