Imperial College London

ProfessorPhilippeFroguel

Faculty of MedicineDepartment of Metabolism, Digestion and Reproduction

Chair in Genomic Medicine
 
 
 
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Contact

 

+44 (0)20 7594 6520p.froguel

 
 
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Assistant

 

Mrs Patricia Murphy +44 (0)20 7594 1603

 
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Location

 

E306Burlington DanesHammersmith Campus

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Summary

 

Publications

Publication Type
Year
to

823 results found

Jungtrakoon Thamtarana P, 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, Ceròn 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 (MDH2) and familial hyperglycemia., J Clin Endocrinol Metab

OBJECTIVE: We set out to identify the genetic cause of hyperglycemia in multigenerational families with an apparent autosomal dominant form of adult-onset diabetes not due to mutations in known monogenic diabetes genes. METHODS: Existing Whole Exome Sequencing (WES) data were used to identify exonic variants segregating with diabetes in 60 families from the US and Italy. Functional studies were carried out in vitro (transfected MIN6-K8 cells) and in vivo (Caenorhabditis elegans) to assess the diabetogenic potential of two variants in the Malate Dehydrogenase 2 (MDH2) gene linked with hyperglycemia in two of the families. RESULTS: A very rare mutation (p.Arg52Cys) in MDH2 strongly segregated with hyperglycemia in one family from the US. An infrequent MDH2 missense variant (p.Val160Met) also showed disease co-segregation in a family from Italy, although with reduced penetrance. In silico, both Arg52Cys and Val160Met were shown to affect MDH2 protein structure and function. In transfected HepG2 cells, both variants significantly increased MDH2 enzymatic activity, thereby decreasing the NAD+/NADH ratio - a change known to affect insulin signaling and secretion. Stable expression of human wild type MDH2 in MIN6-K8 cell lines enhanced glucose- and GLP-1-stimulated insulin secretion. This effect was blunted by the Cys52 or Met160 substitutions. Nematodes carrying equivalent changes at the orthologous positions of the mdh-2 gene showed impaired glucose-stimulated insulin secretion. CONCLUSIONS: Our findings suggest a central role of MDH2 in human glucose homeostasis and indicate that gain of function variants in this gene may be involved in the etiology of familial forms of diabetes.

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

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

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-+, ISSN: 1061-4036

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

Jacob A, Pasquier J, Carapito R, Aurade F, Molitor A, Froguel P, Fakhro K, Halabi N, Viot G, Bahram S, Rafii Aet al., 2020, A de novo synonymous variant inEFTUD2disrupts normal splicing and causes mandibulofacial dysostosis with microcephaly: case report, BMC MEDICAL GENETICS, Vol: 21

Journal article

Khamis A, Canouil M, Marselli L, Boutry R, Suleiman M, Jonckheere N, Schulte AM, Solimena M, Bonnefond A, Van Seuningen I, Ibberson M, Joerns A, Lenzen S, Marchetti P, Froguel Pet al., 2020, Pnliprp1 hypermethylation in human exocrine pancreas reveals a link between diabetes and pancreatic cancer, 56th Annual Meeting of the European-Association-for-the-Study-of-Diabetes (EASD), Publisher: SPRINGER, Pages: S109-S109, ISSN: 0012-186X

Conference paper

Hu M, Cebola I, Carrat G, Nawaz S, Khamis A, Canouil M, Froguel P, Schulte A, Solimena M, Ibberson M, Marchetti P, Gadue P, Hastoy B, McMahon H, Rutter Get al., 2020, Chromatin 3D interaction analysis of the STARD10 locus unveils FCHSD2 as a new regulator of insulin secretion, Publisher: SPRINGER

Working paper

Kahoul Y, Oger F, Montaigne J, Froguel P, Breton C, Annicotte J-Set al., 2020, Emerging Roles for the INK4a/ARF (CDKN2A) Locus in Adipose Tissue: Implications for Obesity and Type 2 Diabetes, BIOMOLECULES, Vol: 10

Journal article

Saeed S, Arslan M, Manzoor J, Din SM, Janjua QM, Ayesha H, Ain Q-T, Inam L, Lobbens S, Vaillant E, Durand E, Derhourhi M, Amanzougarene S, Badreddine A, Berberian L, Gaget S, Khan WI, Butt TA, Bonnefond A, Froguel Pet al., 2020, Genetic Causes of Severe Childhood Obesity: A Remarkably High Prevalence in an Inbred Population of Pakistan, DIABETES, Vol: 69, Pages: 1424-1438, ISSN: 0012-1797

Journal article

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