Genetic approach to unravel the molecular basis of severe early-onset obesity

Bou de Pieri, Francesc

Genetic approach to unravel the molecular basis of severe early-onset obesity

Document Type

Doctoral thesis
Published Version

Author

Bou de Pieri, Francesc

Director

Pérez Jurado, Luis Alberto
Serra Juhé, Clara

Publication Date

2020-12-17

Pages

209 p.

Citation

Bou de Pieri, F. Genetic approach to unravel the molecular basis of severe early-onset obesity. Universitat Pompeu Fabra; 2020. handle: http://hdl.handle.net/10803/670318

This citation was generated automatically.

Doctoral program

Programa de doctorat en Biomedicina

Abstract

Tot i que l’obesitat és clarament deguda a un desequilibri entre la ingesta d’energia i la despesa, i està molt associada a l’estil de vida, es considera una malaltia multifactorial amb una alta heretabilitat (50-75%), probablement superior en els casos d’inici precoç. Diferents estudis la descriuen de forma persistent com una malaltia altament heterogènia a nivell clínic i molecular. Les causes genètiques de la malaltia encara es desconeixen en gran mesura i hi ha una proporció important d’heretabilitat no explicada. En la tesi que es presenta s’han utilitzat diferents estratègies per esbrinar les bases moleculars de l’obesitat severa d’inici precoç. S'han explorat mutacions puntuals i variants en el número de còpies, i s'han realitzat estudis de segregació per a les alteracions rellevants. A més, s'han utilitzat qüestionaris per analitzar els comportaments alimentaris dels portadors. Els resultats dels diferents enfocaments revelen un paper rellevant de les alteracions genètiques en l’obesitat severa d’inici precoç, ja sigui com a mutacions causants de la malaltia o com a factors de susceptibilita
Although obesity is clearly derived from an imbalance between energy intake and expenditure, and highly associated to lifestyle, it is considered a multifactorial disease with high heritability (50-75%), probably higher in early-onset cases. Different studies persistently describe a highly heterogeneous disease at the clinical and molecular levels. The genetic causes underlying the disease are still largely unknown and there is an important proportion of missing heritability. Different approaches have been used in the present thesis to unravel the molecular basis of severe early-onset obesity. Point mutations and copy number variants have been explored, and segregation studies have been performed for relevant alterations. Moreover, questionnaires to analyze the eating behaviors of mutation-carriers have been used. Results from the different approaches reveal a relevant role of genetic alterations in severe early-onset obesity, either as disease-causative mutations or susceptibility factors.