Imperial College London

ProfessorPhilippeFroguel

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Chair in Genomic Medicine
 
 
 
//

Contact

 

+44 (0)20 7594 6520p.froguel

 
 
//

Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
//

Location

 

E306Burlington DanesHammersmith Campus

//

Summary

 

Publications

Publication Type
Year
to

828 results found

Khamis A, Ning L, Balkau B, Bonnefond A, Canouil M, Roussel R, Froguel Pet al., 2022, Epigenetic changes associated with hyperglycaemia exposure in the longitudinal D.E.S.I.R. cohort., Diabetes Metab, Vol: 48

AIM: - Understanding DNA methylation dynamics associated with progressive hyperglycaemia exposure could provide early diagnostic biomarkers and an avenue for delaying type 2 diabetes mellitus (T2DM). We aimed to identify DNA methylation changes during a 6-year period associated with early hyperglycaemia exposure using the longitudinal D.E.S.I.R. COHORT: METHODS: - We selected individuals with progressive hyperglycaemia exposure based on T2DM diagnostic criteria: 27 with long-term exposure, 34 with short-term exposure and 34 normoglycaemic controls. DNA from blood at inclusion and at the 6-year visit was subjected to methylation analysis using 850K methylation-EPIC arrays. A linear mixed model was used to perform an epigenome-wide association study (EWAS) and identify methylated changes associated with hyperglycaemia exposure during a 6-year time-period. RESULTS: - We did not identify differentially methylated sites that reached false discovery rate (FDR)-significance in our cohort. Based on EWAS, we focused our analysis on methylation sites that had a constant effect during the 6 years across the hyperglycaemia groups compared to controls and found the most statistically significant site was the reported cg19693031 probe (TXNIP). We also performed an EWAS with HbA1c, using the inclusion and the 6-year methylation data and did not identify any FDR-significant CpGs. CONCLUSIONS: - Our study reveals that DNA methylation changes are not robustly associated with hyperglycaemia exposure or HbA1c during a short-term period, however, our top loci indicate potential interest and should be replicated in larger cohorts.

Journal article

Lemaitre M, Douillard C, Froguel P, Bonnefond A, Vambergue Aet al., 2022, Management of pregnancy in a patient with congenital hyperinsulinism treated with association of diazoxide/calcium channel blocker, ACTA DIABETOLOGICA, Vol: 59, Pages: 1117-1120, ISSN: 0940-5429

Journal article

Saeed S, Janjua QM, Haseeb A, Khanam R, Durand E, Vaillant E, Ning L, Badreddine A, Berberian L, Boissel M, Amanzougarene S, Canouil M, Derhourhi M, Bonnefond A, Arslan M, Froguel Pet al., 2022, Rare Variant Analysis of Obesity-Associated Genes in Young Adults With Severe Obesity From a Consanguineous Population of Pakistan., Diabetes, Vol: 71, Pages: 694-705

Recent advances in genetic analysis have significantly helped in progressively attenuating the heritability gap of obesity and have brought into focus monogenic variants that disrupt the melanocortin signaling. In a previous study, next-generation sequencing revealed a monogenic etiology in ∼50% of the children with severe obesity from a consanguineous population in Pakistan. Here we assess rare variants in obesity-causing genes in young adults with severe obesity from the same region. Genomic DNA from 126 randomly selected young adult obese subjects (BMI 37.2 ± 0.3 kg/m2; age 18.4 ± 0.3 years) was screened by conventional or augmented whole-exome analysis for point mutations and copy number variants (CNVs). Leptin, insulin, and cortisol levels were measured by ELISA. We identified 13 subjects carrying 13 different pathogenic or likely pathogenic variants in LEPR, PCSK1, MC4R, NTRK2, POMC, SH2B1, and SIM1. We also identified for the first time in the human, two homozygous stop-gain mutations in ASNSD1 and IFI16 genes. Inactivation of these genes in mouse models has been shown to result in obesity. Additionally, we describe nine homozygous mutations (seven missense, one stop-gain, and one stop-loss) and four copy-loss CNVs in genes or genomic regions previously linked to obesity-associated traits by genome-wide association studies. Unexpectedly, in contrast to obese children, pathogenic mutations in LEP and LEPR were either absent or rare in this cohort of young adults. High morbidity and mortality risks and social disadvantage of children with LEP or LEPR deficiency may in part explain this difference between the two cohorts.

Journal article

Tobi EW, Juvinao-Quintero DL, Ronkainen J, Ott R, Alfano R, Canouil M, Geurtsen ML, Khamis A, Küpers LK, Lim IY, Perron P, Pesce G, Tuhkanen J, Starling AP, Andrew T, Binder E, Caiazzo R, Chan JKY, Gaillard R, Gluckman PD, Keikkala E, Karnani N, Mustaniemi S, Nawrot TS, Pattou F, Plusquin M, Raverdy V, Tan KH, Tzala E, Raikkonen K, Winkler C, Ziegler A-G, Annesi-Maesano I, Bouchard L, Chong YS, Dabelea D, Felix JF, Heude B, Jaddoe VWV, Lahti J, Reimann B, Vääräsmäki M, Bonnefond A, Froguel P, Hummel S, Kajantie E, Jarvelin M-R, Steegers-Theunissen RPM, Howe CG, Hivert M-F, Sebert Set al., 2022, Maternal Glycemic Dysregulation During Pregnancy and Neonatal Blood DNA Methylation: Meta-analyses of Epigenome-Wide Association Studies., Diabetes Care, Vol: 45, Pages: 614-623

OBJECTIVE: Maternal glycemic dysregulation during pregnancy increases the risk of adverse health outcomes in her offspring, a risk thought to be linearly related to maternal hyperglycemia. It is hypothesized that changes in offspring DNA methylation (DNAm) underline these associations. RESEARCH DESIGN AND METHODS: To address this hypothesis, we conducted fixed-effects meta-analyses of epigenome-wide association study (EWAS) results from eight birth cohorts investigating relationships between cord blood DNAm and fetal exposure to maternal glucose (Nmaximum = 3,503), insulin (Nmaximum = 2,062), and area under the curve of glucose (AUCgluc) following oral glucose tolerance tests (Nmaximum = 1,505). We performed lookup analyses for identified cytosine-guanine dinucleotides (CpGs) in independent observational cohorts to examine associations between DNAm and cardiometabolic traits as well as tissue-specific gene expression. RESULTS: Greater maternal AUCgluc was associated with lower cord blood DNAm at neighboring CpGs cg26974062 (β [SE] -0.013 [2.1 × 10-3], P value corrected for false discovery rate [PFDR] = 5.1 × 10-3) and cg02988288 (β [SE]-0.013 [2.3 × 10-3], PFDR = 0.031) in TXNIP. These associations were attenuated in women with GDM. Lower blood DNAm at these two CpGs near TXNIP was associated with multiple metabolic traits later in life, including type 2 diabetes. TXNIP DNAm in liver biopsies was associated with hepatic expression of TXNIP. We observed little evidence of associations between either maternal glucose or insulin and cord blood DNAm. CONCLUSIONS: Maternal hyperglycemia, as reflected by AUCgluc, was associated with lower cord blood DNAm at TXNIP. Associations between DNAm at these CpGs and metabolic traits in subsequent lookup analyses suggest that these may be candidate loci to investigate in future causal and mediation analyses.

Journal article

Le Collen L, Delemer B, Spodenkiewicz M, Lefebvre PC, Durand E, Vaillant E, Badreddine A, Derhourhi M, Mouhoub TA, Jouret G, Juttet P, Souchon PF, Vaxillaire M, Froguel P, Bonnefond A, Fenzy MDet al., 2022, Compound genetic etiology in a patient with a syndrome including diabetes, intellectual deficiency and distichiasis, ORPHANET JOURNAL OF RARE DISEASES, Vol: 17

Journal article

Thamtarana PJ, Marucci A, Pannone L, Bonnefond A, Pezzilli S, Biagini T, Buranasupkajorn P, Hastings T, Mendonca C, Marselli L, Di Paola R, Abubakar Z, Mercuri L, Alberico F, Flex E, Ceron J, Porta-de-la-Riva M, Ludovico O, Carella M, Martinelli S, Marchetti P, Mazza T, Froguel P, Trischitta V, Doria A, Prudente Set al., 2021, Gain of Function of Malate Dehydrogenase 2 and Familial Hyperglycemia, JOURNAL OF CLINICAL ENDOCRINOLOGY & METABOLISM, Vol: 107, Pages: 668-684, ISSN: 0021-972X

Journal article

Meulebrouck S, Queniat G, Baron M, Canouil M, Derhourhi M, Balkau B, Charpentier G, Franc S, Marre M, Roussel R, Scharfmann R, Froguel P, Bonnefond Aet al., 2021, Mirror effects of rare OPRD1 variants on the aetiology of type 2 diabetes and obesity, Publisher: SPRINGER, Pages: 109-109, ISSN: 0012-186X

Conference paper

Khamis A, Canouil M, Keikkala E, Hummel S, Bonnefond A, Delahaye F, Vaarasmaki M, Jarvelin M-R, Sebert S, Kajantie E, Froguel P, Andrew Tet al., 2021, Both gestational diabetes exposure and maternal methylome interaction impacts offspring epigenetic signature, Publisher: SPRINGER, Pages: 143-144, ISSN: 0012-186X

Conference paper

Slieker RC, Donnelly LA, Lopez-Noriega L, Giordano GN, Akerlund M, Pavo I, Lyssenko V, Quigley CL, Groop L, Ibberson M, Beulens JWJ, ' t Hart LM, Pearson ER, Rutter GAet al., 2021, Novel biomarkers for glycaemic deterioration in type 2 diabetes: an IMI RHAPSODY study, Publisher: SPRINGER, Pages: 108-108, ISSN: 0012-186X

Conference paper

Canouil M, Khamis A, Keikkala E, Hummel S, Lobbens S, Bonnefond A, Delahaye F, Tzala E, Mustaniemi S, Vaarasmaki M, Jarvelin M-R, Sebert S, Kajantie E, Froguel P, Andrew Tet al., 2021, Epigenome-Wide Association Study Reveals Methylation Loci Associated With Offspring Gestational Diabetes Mellitus Exposure and Maternal Methylome, DIABETES CARE, Vol: 44, Pages: 1992-1999, ISSN: 0149-5992

Journal article

Hegron A, Huh E, Deupi X, Sokrat B, Gao W, Le Gouill C, Canouil M, Boissel M, Charpentier G, Roussel R, Balkau B, Froguel P, Plouffe B, Bonnefond A, Lichtarge O, Jockers R, Bouvier Met al., 2021, Identification of Key Regions Mediating Human Melatonin Type 1 Receptor Functional Selectivity Revealed by Natural Variants, ACS PHARMACOLOGY & TRANSLATIONAL SCIENCE, Vol: 4, Pages: 1614-1627

Journal article

De T, Goncalves A, Speed D, Froguel P, Gaffney DJ, Johnson MR, Jarvelin M-R, Coin LJMet al., 2021, Signatures of TSPAN8 variants associated with human metabolic regulation and diseases, ISCIENCE, Vol: 24

Journal article

Voisin S, Jacques M, Landen S, Harvey NR, Haupt LM, Griffiths LR, Gancheva S, Ouni M, Jahnert M, Ashton KJ, Coffey VG, Thompson J-LM, Doering TM, Gabory A, Junien C, Caiazzo R, Verkindt H, Raverdy V, Pattou F, Froguel P, Craig JM, Blocquiaux S, Thomis M, Sharples AP, Schuermann A, Roden M, Horvath S, Eynon Net al., 2021, Meta-analysis of genome-wide DNA methylation and integrative omics of age in human skeletal muscle, JOURNAL OF CACHEXIA SARCOPENIA AND MUSCLE, Vol: 12, Pages: 1064-1078, ISSN: 2190-5991

Journal article

Chen J, Spracklen CN, Marenne G, Varshney A, Corbin LJ, Luan J, Willems SM, Wu Y, Zhang X, Horikoshi M, Boutin TS, Magi R, Waage J, Li-Gao R, Chan KHK, Yao J, Anasanti MD, Chu AY, Claringbould A, Heikkinen J, Hong J, Hottenga J-J, Huo S, Kaakinen MA, Louie T, Maerz W, Moreno-Macias H, Ndungu A, Nelson SC, Nolte IM, North KE, Raulerson CK, Ray D, Rohde R, Rybin D, Schurmann C, Sim X, Southam L, Stewart ID, Wang CA, Wang Y, Wu P, Zhang W, Ahluwalia TS, Appel EVR, Bielak LF, Brody JA, Burtt NP, Cabrera CP, Cade BE, Chai JF, Chai X, Chang L-C, Chen C-H, Chen BH, Chitrala KN, Chiu Y-F, de Haan HG, Delgado GE, Demirkan A, Duan Q, Engmann J, Fatumo SA, Gayan J, Giulianini F, Gong JH, Gustafsson S, Hai Y, Hartwig FP, He J, Heianza Y, Huang T, Huerta-Chagoya A, Hwang MY, Jensen RA, Kawaguchi T, Kentistou KA, Kim YJ, Kleber ME, Kooner IK, Lai S, Lange LA, Langefeld CD, Lauzon M, Li M, Ligthart S, Liu J, Loh M, Long J, Lyssenko V, Mangino M, Marzi C, Montasser ME, Nag A, Nakatochi M, Noce D, Noordam R, Pistis G, Preuss M, Raffield L, Rasmussen-Torvik LJ, Rich SS, Robertson NR, Rueedi R, Ryan K, Sanna S, Saxena R, Schraut KE, Sennblad B, Setoh K, Smith AV, Sparso T, Strawbridge RJ, Takeuchi F, Tan J, Trompet S, van den Akker E, van der Most PJ, Verweij N, Vogel M, Wang H, Wang C, Wang N, Warren HR, Wen W, Wilsgaard T, Wong A, Wood AR, Xie T, Zafarmand MH, Zhao J-H, Zhao W, Amin N, Arzumanyan Z, Astrup A, Bakker SJL, Baldassarre D, Beekman M, Bergman RN, Bertoni A, Blueher M, Bonnycastle LL, Bornstein SR, Bowden DW, Cai Q, Campbell A, Campbell H, Chang YC, de Geus EJC, Dehghan A, Du S, Eiriksdottir G, Farmaki AE, Franberg M, Fuchsberger C, Gao Y, Gjesing AP, Goel A, Han S, Hartman CA, Herder C, Hicks AA, Hsieh C-H, Hsueh WA, Ichihara S, Igase M, Ikram MA, Johnson WC, Jorgensen ME, Joshi PK, Kalyani RR, Kandeel FR, Katsuya T, Khor CC, Kiess W, Kolcic I, Kuulasmaa T, Kuusisto J, Lall K, Lam K, Lawlor DA, Lee NR, Lemaitre RN, Li H, Lin S-Y, Lindstrom J, Linneberg A, Liu J, Lorenzoet al., 2021, The trans-ancestral genomic architecture of glycemic traits, Nature Genetics, Vol: 53, Pages: 840-860, ISSN: 1061-4036

Glycemic traits are used to diagnose and monitor type 2 diabetes and cardiometabolic health. To date, most genetic studies of glycemic traits have focused on individuals of European ancestry. Here we aggregated genome-wide association studies comprising up to 281,416 individuals without diabetes (30% non-European ancestry) for whom fasting glucose, 2-h glucose after an oral glucose challenge, glycated hemoglobin and fasting insulin data were available. Trans-ancestry and single-ancestry meta-analyses identified 242 loci (99 novel; P < 5 × 10−8), 80% of which had no significant evidence of between-ancestry heterogeneity. Analyses restricted to individuals of European ancestry with equivalent sample size would have led to 24 fewer new loci. Compared with single-ancestry analyses, equivalent-sized trans-ancestry fine-mapping reduced the number of estimated variants in 99% credible sets by a median of 37.5%. Genomic-feature, gene-expression and gene-set analyses revealed distinct biological signatures for each trait, highlighting different underlying biological pathways. Our results increase our understanding of diabetes pathophysiology by using trans-ancestry studies for improved power and resolution.

Journal article

Paccoud R, Saint-Laurent C, Piccolo E, Tajan M, Dortignac A, Pereira O, Le Gonidec S, Baba I, Gelineau A, Askia H, Branchereau M, Charpentier J, Personnaz J, Branka S, Auriau J, Deleruyelle S, Canouil M, Beton N, Salles J-P, Tauber M, Weill J, Froguel P, Neel BG, Araki T, Heymes C, Burcelin R, Castan I, Valet P, Dray C, Gautier EL, Edouard T, Pradere J-P, Yart Aet al., 2021, SHP2 drives inflammation-triggered insulin resistance by reshaping tissue macrophage populations, SCIENCE TRANSLATIONAL MEDICINE, Vol: 13, ISSN: 1946-6234

Journal article

Porcu E, Gilardi F, Darrous L, Yengo L, Bararpour N, Gasser M, Marques-Vidal P, Froguel P, Waeber G, Thomas A, Kutalik Zet al., 2021, Triangulating evidence from longitudinal and Mendelian randomization studies of metabolomic biomarkers for type 2 diabetes, SCIENTIFIC REPORTS, Vol: 11, ISSN: 2045-2322

Journal article

Hu M, Cebola I, Carrat G, Jiang S, Nawaz S, Khamis A, Canouil M, Froguel P, Schulte A, Solimena M, Ibberson M, Marchetti P, Cardenas-Diaz FL, Gadue PJ, Hastoy B, Almeida-Souza L, McMahon H, Rutter GAet al., 2021, Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a regulator of insulin secretion., Cell Research, Vol: 34, Pages: 1-1, ISSN: 1001-0602

Using chromatin conformation capture, we show that an enhancer cluster in the STARD10 type 2 diabetes (T2D) locus forms a defined 3-dimensional (3D) chromatin domain. A 4.1-kb region within this locus, carrying 5 T2D-associated variants, physically interacts with CTCF-binding regions and with an enhancer possessing strong transcriptional activity. Analysis of human islet 3D chromatin interaction maps identifies the FCHSD2 gene as an additional target of the enhancer cluster. CRISPR-Cas9-mediated deletion of the variant region, or of the associated enhancer, from human pancreas-derived EndoC-βH1 cells impairs glucose-stimulated insulin secretion. Expression of both STARD10 and FCHSD2 is reduced in cells harboring CRISPR deletions, and lower expression of STARD10 and FCHSD2 is associated, the latter nominally, with the possession of risk variant alleles in human islets. Finally, CRISPR-Cas9-mediated loss of STARD10 or FCHSD2, but not ARAP1, impairs regulated insulin secretion. Thus, multiple genes at the STARD10 locus influence β cell function.

Journal article

Lagou V, Mägi R, Hottenga J-J, Grallert H, Perry JRB, Bouatia-Naji N, Marullo L, Rybin D, Jansen R, Min JL, Dimas AS, Ulrich A, Zudina L, Gådin JR, Jiang L, Faggian A, Bonnefond A, Fadista J, Stathopoulou MG, Isaacs A, Willems SM, Navarro P, Tanaka T, Jackson AU, Montasser ME, O'Connell JR, Bielak LF, Webster RJ, Saxena R, Stafford JM, Pourcain BS, Timpson NJ, Salo P, Shin S-Y, Amin N, Smith AV, Li G, Verweij N, Goel A, Ford I, Johnson PCD, Johnson T, Kapur K, Thorleifsson G, Strawbridge RJ, Rasmussen-Torvik LJ, Esko T, Mihailov E, Fall T, Fraser RM, Mahajan A, Kanoni S, Giedraitis V, Kleber ME, Silbernagel G, Meyer J, Müller-Nurasyid M, Ganna A, Sarin A-P, Yengo L, Shungin D, Luan J, Horikoshi M, An P, Sanna S, Boettcher Y, Rayner NW, Nolte IM, Zemunik T, Iperen EV, Kovacs P, Hastie ND, Wild SH, McLachlan S, Campbell S, Polasek O, Carlson O, Egan J, Kiess W, Willemsen G, Kuusisto J, Laakso M, Dimitriou M, Hicks AA, Rauramaa R, Bandinelli S, Thorand B, Liu Y, Miljkovic I, Lind L, Doney A, Perola M, Hingorani A, Kivimaki M, Kumari M, Bennett AJ, Groves CJ, Herder C, Koistinen HA, Kinnunen L, Faire UD, Bakker SJL, Uusitupa M, Palmer CNA, Jukema JW, Sattar N, Pouta A, Snieder H, Boerwinkle E, Pankow JS, Magnusson PK, Krus U, Scapoli C, de Geus EJCN, Blüher M, Wolffenbuttel BHR, Province MA, Abecasis GR, Meigs JB, Hovingh GK, Lindström J, Wilson JF, Wright AF, Dedoussis GV, Bornstein SR, Schwarz PEH, Tönjes A, Winkelmann BR, Boehm BO, März W, Metspalu A, Price JF, Deloukas P, Körner A, Lakka TA, Keinanen-Kiukaanniemi SM, Saaristo TE, Bergman RN, Tuomilehto J, Wareham NJ, Langenberg C, Männistö S, Franks PW, Hayward C, Vitart V, Kaprio J, Visvikis-Siest S, Balkau B, Altshuler D, Rudan I, Stumvoll M, Campbell H, van Duijn CM, Gieger C, Illig T, Ferrucci L, Pedersen NL, Pramstaller PP, Boehnke M, Frayling TM, Shuldiner AR, Peyser PA, Kardia SLR, Palmer LJ, Penninx BW, Meneton P, Harris TB, Navis G, Harst PVD, Smith GD, Forouhi NG, Loos RJF, Salomaa V, Soranzo N, Boomsma DIet al., 2021, Publisher Correction: Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability., Nat Commun, Vol: 12

Journal article

Bonnefond A, Froguel P, 2021, Clustering for a better prediction of type 2 diabetes mellitus, NATURE REVIEWS ENDOCRINOLOGY, Vol: 17, Pages: 193-194, ISSN: 1759-5029

Journal article

Lagou V, Maegi R, Hottenga J-J, Grallert H, Perry JRB, Bouatia-Naji N, Marullo L, Rybin D, Jansen R, Min JL, Dimas AS, Ulrich A, Zudina L, Gadin JR, Jiang L, Faggian A, Bonnefond A, Fadista J, Stathopoulou MG, Isaacs A, Willems SM, Navarro P, Tanaka T, Jackson AU, Montasser ME, O'Connell JR, Bielak LF, Webster RJ, Saxena R, Stafford JM, Pourcain BS, Timpson NJ, Salo P, Shin S-Y, Amin N, Smith AV, Li G, Verweij N, Goel A, Ford I, Johnson PCD, Johnson T, Kapur K, Thorleifsson G, Strawbridge RJ, Rasmussen-Torvik LJ, Esko T, Mihailov E, Fall T, Fraser RM, Mahajan A, Kanoni S, Giedraitis V, Kleber ME, Silbernagel G, Meyer J, Mueller-Nurasyid M, Ganna A, Sarin A-P, Yengo L, Shungin D, Luan J, Horikoshi M, An P, Sanna S, Boettcher Y, Rayner NW, Nolte IM, Zemunik T, Iperen EV, Kovacs P, Hastie ND, Wild SH, McLachlan S, Campbell S, Polasek O, Carlson O, Egan J, Kiess W, Willemsen G, Kuusisto J, Laakso M, Dimitriou M, Hicks AA, Rauramaa R, Bandinelli S, Thorand B, Liu Y, Miljkovic I, Lind L, Doney A, Perola M, Hingorani A, Kivimaki M, Kumari M, Bennett AJ, Groves CJ, Herder C, Koistinen HA, Kinnunen L, Faire UD, Bakker SJL, Uusitupa M, Palmer CNA, Jukema JW, Sattar N, Pouta A, Snieder H, Boerwinkle E, Pankow JS, Magnusson PK, Krus U, Scapoli C, de Geus EJCN, Blueher M, Wolffenbuttel BHR, Province MA, Abecasis GR, Meigs JB, Hovingh GK, Lindstroem J, Wilson JF, Wright AF, Dedoussis GV, Bornstein SR, Schwarz PEH, Toenjes A, Winkelmann BR, Boehm BO, Maerz W, Metspalu A, Price JF, Deloukas P, Koerner A, Lakka TA, Keinanen-Kiukaanniemi SM, Saaristo TE, Bergman RN, Tuomilehto J, Wareham NJ, Langenberg C, Maennistoe S, Franks PW, Hayward C, Vitart V, Kaprio J, Visvikis-Siest S, Balkau B, Altshuler D, Rudan I, Stumvoll M, Campbell H, van Duijn CM, Gieger C, Illig T, Ferrucci L, Pedersen NL, Pramstaller PP, Boehnke M, Frayling TM, Shuldiner AR, Peyser PA, Kardia SLR, Palmer LJ, Penninx BW, Meneton P, Harris TB, Navis G, Harst PVD, Smith GD, Forouhi NG, Loos RJF, Salomaa V, Soranzo N Bet al., 2021, Sex-dimorphic genetic effects and novel loci for fasting glucose and insulin variability, NATURE COMMUNICATIONS, Vol: 12, ISSN: 2041-1723

Journal article

Vaxillaire M, Bonnefond A, Liatis S, Hachmi LBS, Jotic A, Boissel M, Gaget S, Durand E, Vaillant E, Derhourhi M, Canouil M, Larcher N, Allegaert F, Medlej R, Chadli A, Belhadj A, Chaieb M, Raposo J-F, Ilkova H, Loizou D, Lalic N, Vassallo J, Marre M, Froguel Pet al., 2021, Monogenic diabetes characteristics in a transnational multicenter study from Mediterranean countries, DIABETES RESEARCH AND CLINICAL PRACTICE, Vol: 171, ISSN: 0168-8227

Journal article

Saeed S, Arslan M, Manzoor J, Janjua QM, Ayesha H, Durand E, Khan WI, Butt TA, Bonnefond A, Froguel Pet al., 2020, Genetic aetiology of early onset severe obesity revealed in half of the affected cases from a consanguineous population of Pakistan, Publisher: SPRINGERNATURE, Pages: 568-569, ISSN: 1018-4813

Conference paper

Vaxillaire M, Bonnefond A, Liatis S, Hachmi LBS, Jotic A, Boissel M, Gaget S, Durand E, Vaillant E, Derhourhi M, Larcher N, Allegaert F, Medlej R, Chadli A, Arbouche Z, Belhadj A, Chaieb M, Raposo J, Ilkova H, Loizou D, Lalic N, Vassallo J, Marre M, Froguel Pet al., 2020, Monogenic diabetes gene screening in a transnational multicenter study from eleven countries of the Mediterranean area, Publisher: SPRINGERNATURE, Pages: 683-684, ISSN: 1018-4813

Conference paper

Marselli L, Piron A, Suleiman M, Colli ML, Yi X, Khamis A, Carrat GR, Rutter GA, Bugliani M, Giusti L, Ronci M, Ibberson M, Turatsinze J-V, Boggi U, De Simone P, De Tata V, Lopes M, Nasteska D, De Luca C, Tesi M, Bosi E, Singh P, Campani D, Schulte AM, Solimena M, Hecht P, Rady B, Bakaj I, Pocai A, Norquay L, Thorens B, Canouil M, Froguel P, Eizirik DL, Cnop M, Marchetti Pet al., 2020, Persistent or transient human β cell dysfunction induced by metabolic stress: specific signatures and shared gene expression with type 2 diabetes, Cell Reports, Vol: 33, ISSN: 2211-1247

Pancreatic β cell failure is key to type 2 diabetes (T2D) onset and progression. Here, we assess whether human β cell dysfunction induced by metabolic stress is reversible, evaluate the molecular pathways underlying persistent or transient damage, and explore the relationships with T2D islet traits. Twenty-six islet preparations are exposed to several lipotoxic/glucotoxic conditions, some of which impair insulin release, depending on stressor type, concentration, and combination. The reversal of dysfunction occurs after washout for some, although not all, of the lipoglucotoxic insults. Islet transcriptomes assessed by RNA sequencing and expression quantitative trait loci (eQTL) analysis identify specific pathways underlying β cell failure and recovery. Comparison of a large number of human T2D islet transcriptomes with those of persistent or reversible β cell lipoglucotoxicity show shared gene expression signatures. The identification of mechanisms associated with human β cell dysfunction and recovery and their overlap with T2D islet traits provide insights into T2D pathogenesis, fostering the development of improved β cell-targeted therapeutic strategies.

Journal article

Bar N, Korem T, Weissbrod O, Zeevi D, Rothschild D, Leviatan S, Kosower N, Lotan-Pompan M, Weinberger A, Le Roy CI, Menni C, Visconti A, Falchi M, Spector TD, Adamski J, Franks PW, Pedersen O, Segal Eet al., 2020, A reference map of potential determinants for the human serum metabolome, NATURE, Vol: 588, Pages: 135-140, ISSN: 0028-0836

Journal article

El Shamieh S, Stathopoulou MG, Bonnefond A, Ndiaye NC, Lecoeur C, Meyre D, Dade S, Chedid P, Salami A, Shahabi P, Dedoussis G, Froguel P, Visvikis-Siest Set al., 2020, Obesity status modifies the association between rs7556897T > C in the intergenic region SLC19A3-CCL20 and blood pressure in French children, CLINICAL CHEMISTRY AND LABORATORY MEDICINE, Vol: 58, Pages: 1819-1827, ISSN: 1434-6621

Journal article

Imam A, Winnebeck EC, Buchholz N, Froguel P, Bonnefond A, Solimena M, Ivanova A, Bouvier M, Plouffe B, Charpentier G, Karamitri A, Jockers R, Roenneberg T, Vetter Cet al., 2020, Circadian, Sleep and Caloric Intake Phenotyping in Type 2 Diabetes Patients With Rare Melatonin Receptor 2 Mutations and Controls: A Pilot Study, FRONTIERS IN PHYSIOLOGY, Vol: 11, ISSN: 1664-042X

Journal article

Baron M, Froguel P, Bonnefond A, 2020, Something new in the genetics of monogenic obesity and its insights into pathophysiology, M S-MEDECINE SCIENCES, Vol: 36, Pages: 859-865, ISSN: 0767-0974

Journal article

Bonnefond A, Boissel M, Bolze A, Durand E, Toussaint B, Vaillant E, Gaget S, De Graeve F, Dechaume A, Allegaert F, Le Guilcher D, Yengo L, Dhennin V, Borys J-M, Lu JT, Cirulli ET, Elhanan G, Roussel R, Balkau B, Marre M, Franc S, Charpentier G, Vaxillaire M, Canouil M, Washington NL, Grzymski JJ, Froguel Pet al., 2020, Pathogenic variants in actionable MODY genes are associated with type 2 diabetes, NATURE METABOLISM, Vol: 2, Pages: 1126-+

Journal article

Vogelezang S, Bradfield JP, Ahluwalia TS, Curtin JA, Lakka TA, Grarup N, Scholz M, van der Most PJ, Monnereau C, Stergiakouli E, Heiskala A, Horikoshi M, Fedko IO, Vilor-Tejedor N, Cousminer DL, Standl M, Wang CA, Viikari J, Geller F, iniguez C, Pitkanen N, Chesi A, Bacelis J, Yengo L, Torrent M, Ntalla I, Helgeland O, Selzam S, Vonk JM, Zafarmand MH, Heude B, Farooqi IS, Alyass A, Beaumont RN, Have CT, Rzehak P, Bilbao JR, Schnurr TM, Barroso I, Bonnelykke K, Beilin LJ, Carstensen L, Charles M-A, Chawes B, Clement K, Closa-Monasterolo R, Custovic A, Eriksson JG, Escribano J, Groen-Blokhuis M, Grote V, Gruszfeld D, Hakonarson H, Hansen T, Hattersley AT, Hollensted M, Hottenga J-J, Hypponen E, Johansson S, Joro R, Kahonen M, Karhunen V, Kiess W, Knight BA, Koletzko B, Kuehnapfel A, Landgraf K, Langhendries J-P, Lehtimaki T, Leinonen JT, Li A, Lindi V, Lowry E, Bustamante M, Medina-Gomez C, Melbye M, Michaelsen KF, Morgen CS, Mori TA, Nielsen TRH, Niinikoski H, Oldehinkel AJ, Pahkala K, Panoutsopoulou K, Pedersen O, Pennell CE, Power C, Reijneveld SA, Rivadeneira F, Simpson A, Sly PD, Stokholm J, Teo KK, Thiering E, Timpson NJ, Uitterlinden AG, van Beijsterveldt CEM, van Schaik BDC, Vaudel M, Verduci E, Vinding RK, Vogel M, Zeggini E, Sebert S, Lind MV, Brown CD, Santa-Marina L, Reischl E, Frithioff-Bojsoe C, Meyre D, Wheeler E, Ong K, Nohr EA, Vrijkotte TGM, Koppelman GH, Plomin R, Njolstad PR, Dedoussis GD, Froguel P, Sorensen TIA, Jacobsson B, Freathy RM, Zemel BS, Raitakari O, Vrijheid M, Feenstra B, Lyytikainen L-P, Snieder H, Kirsten H, Holt PG, Heinrich J, Widen E, Sunyer J, Boomsma DI, Jarvelin M-R, Koerner A, Davey Smith G, Holm J-C, Atalay M, Murray C, Bisgaard H, McCarthy MI, Jaddoe VWV, Grant SFA, Felix JFet al., 2020, Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits, PLoS Genetics, Vol: 16, Pages: 1-26, ISSN: 1553-7390

The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown. We performed a genome-wide association study meta-analysis of BMI in 61,111 children aged between 2 and 10 years. Twenty-five independent loci reached genome-wide significance in the combined discovery and replication analyses. Two of these, located near NEDD4L and SLC45A3, have not previously been reported in relation to either childhood or adult BMI. Positive genetic correlations of childhood BMI with birth weight and adult BMI, waist-to-hip ratio, diastolic blood pressure and type 2 diabetes were detected (Rg ranging from 0.11 to 0.76, P-values <0.002). A negative genetic correlation of childhood BMI with age at menarche was observed. Our results suggest that the biological processes underlying childhood BMI largely, but not completely, overlap with those underlying adult BMI. The well-known observational associations of BMI in childhood with cardio-metabolic diseases in adulthood may reflect partial genetic overlap, but in light of previous evidence, it is also likely that they are explained through phenotypic continuity of BMI from childhood into adulthood.

Journal article

This data is extracted from the Web of Science and reproduced under a licence from Thomson Reuters. You may not copy or re-distribute this data in whole or in part without the written consent of the Science business of Thomson Reuters.

Request URL: http://wlsprd.imperial.ac.uk:80/respub/WEB-INF/jsp/search-html.jsp Request URI: /respub/WEB-INF/jsp/search-html.jsp Query String: respub-action=search.html&id=00385224&limit=30&person=true