Abstract Search

ey0016.11-1 | New Insights into Body Weight Regulation | ESPEYB16

11.1. Genetic architecture of human thinness compared to severe obesity

F Riveros-McKay , V Mistry , R Bounds , A Hendricks , JM Keogh , H Thomas , E Henning , LJ Corbin , Understanding Society Scientific Group , S O'Rahilly , E Zeggini , E Wheeler , I Barroso , IS Farooqi

To read the full abstract: PLoS Genet. 2019; 15(1):e1007603.This genome wide association study reveals new insights into the genetic basis of thinness by investigating a large cohort of healthy persistently thin individuals. In the past, it has been speculated that inheritance of thinness may constitute a protective factor against environmental factors disposing to obesity (1). Neverthel...

0 shares

ey0019.15-3 | Obesity | ESPEYB19

15.3. Obesity-associated GNAS mutations and the melanocortin pathway

E Mendes de Oliveira , JM Keogh , F Talbot , E Henning , R Ahmed , A Perdikari , R Bounds , N Wasiluk , V Ayinampudi , I Barroso , J Mokrosinski , D Jyothish , S Lim , S Gupta , M Kershaw , C Matei , P Partha , T Randell , A McAulay , LC Wilson , T Cheetham , EC Crowne , P Clayton , IS Farooqi

N Engl J Med. 2021;385(17):1581-92. doi: 10.1056/NEJMoa2103329.PubMed ID: 34614324Brief Summary: The authors performed whole exome sequencing in 2548 children with severe obesity and identified 22 GNAS mutation carriers, almost all of which disrupted melanocortin 4 receptor (MC4R) signaling.The gene GNAS encodes the stimulatory G-protein alpha subunit pr...

1 shares

ey0016.2-7 | Neonatal Diabetes Mellitus | ESPEYB16

2.7. A specific CNOT1 mutation results in a novel syndrome of pancreatic agenesis and holoprosencephaly through impaired pancreatic and neurological development

E De Franco , RA Watson , WJ Weninger , CC Wong , SE Flanagan , R Caswell , A Green , C Tudor , CJ Lelliott , SH Geyer , B Maurer-Gesek , LF Reissig , H Lango Allen , A Caliebe , R Siebert , PM Holterhus , A Deeb , F Prin , R Hilbrands , H Heimberg , S Ellard , AT Hattersley , I Barroso

To read the full abstract: Am J Hum Genet. 2019 May 2;104(5):985989.This study reports the identification of a novel gene that is involved in the regulation of the pancreatic development.Understanding the molecular mechanisms of pancreatic development is important, for example to guide the progress of beta-cell replacement therapy for patients with Type 1 dia...

0 shares

ey0016.11-3 | New Insights into Body Weight Regulation | ESPEYB16

11.3. Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis

Y Yang , AA van der Klaauw , L Zhu , TM Cacciottolo , Y He , LKJ Stadler , C Wang , P Xu , K Saito , A Jr. Hinton , X Yan , JM Keogh , E Henning , MC Banton , AE Hendricks , EG Bochukova , V Mistry , KL Lawler , L Liao , J Xu , S O'Rahilly , Q Tong , UK10K Consortium , I Barroso , BW O'Malley , IS Farooqi , Y Xu

To read the full abstract: Nat Comm 2019; 10(1): 1718Steroid receptor coactivator (SRC)-1 mediates nuclear hormone receptors and transcription factor-dependent transcription (1), and interacts with STAT3 (2) an important mediator of leptin-induced POMC expression and hence satiety (3). Src-1 knockout mice are obese (4), however, the underlying mechanism is unclear. In a...

0 shares

ey0020.9-6 | Advances in Understanding Central Weight Regulation and Behaviour | ESPEYB20

9.6. Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior

Y He , B Brouwers , H Liu , K Lawler , EM de Oliveira , DK Lee , Y Yang , AR Cox , JM Keogh , E Henning , R Bounds , A Perdikari , V Ayinampudi , C Wang , M Yu , L Tu , N Zhang , N Yin , J Han , NA Scarcelli , Z Yan , KM Conde , C Potts , JC Bean , M Wang , SM Hartig , L Liao , J Xu , I Barroso , J Mokrosinski , Y Xu , IS Farooqi

Brief summary: This collaborative study identified 13 monoallelic rare loss-of-function (LoF) variants in the serotonin 2C receptor (HTR2C) gene in 19 unrelated individuals with hyperphagia, severe early-onset obesity, and some degree of maladaptive behaviour. The authors used exome sequencing in 2548 individuals with severe obesity and 1117 control individuals without obesity. They found that HTR2C variants cause monogenic obesity by demonstrating t...

1 shares

ey0021.11-10 | Genetic Risk Score and New Genes | ESPEYB21

11.10. Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease

Y Zhao , M Chukanova , KA Kentistou , Z Fairhurst-Hunter , AM Siegert , RY Jia , GKC Dowsett , EJ Gardner , K Lawler , FR Day , LR Kaisinger , YCL Tung , Lam B Yee Hong , HJC Chen , Q Wang , J Berumen-Campos , P Kuri-Morales , R Tapia-Conyer , J Alegre-Diaz , I Barroso , J Emberson , JM Torres , R Collins , D Saleheen , KR Smith , DS Paul , F Merkle , IS Farooqi , NJ Wareham , S Petrovski , S O'Rahilly , KK Ong , GSH Yeo , JRB Perry

Brief Summary: This exome-wide association study conducted in the UK Biobank cohort (n=454 787) and in two non-European cohorts, the Mexican MCPS cohort (n=141 046) and the Pakistani PGR cohort (n=37 800), identified a association between rare protein-truncating variants (PTVs) in the APBA1 and the BSN genes and adult-onset obesity, suggesting two new genes as possible causes for monogenic obesity. Rare PTVs in BSN were also associated with Type 2 di...

0 shares

ESPE Yearbook of Paediatric Endocrinology

11.1. Genetic architecture of human thinness compared to severe obesity

15.3. Obesity-associated GNAS mutations and the melanocortin pathway

2.7. A specific CNOT1 mutation results in a novel syndrome of pancreatic agenesis and holoprosencephaly through impaired pancreatic and neurological development

11.3. Steroid receptor coactivator-1 modulates the function of Pomc neurons and energy homeostasis

9.6. Human loss-of-function variants in the serotonin 2C receptor associated with obesity and maladaptive behavior

11.10. Protein-truncating variants in BSN are associated with severe adult-onset obesity, type 2 diabetes and fatty liver disease

BiosciAbstracts