Title :

The expression of genes in top obesity-associated loci is enriched in insula and substantia nigra brain regions involved in addiction and reward.

Author(s) :

Ndiaye, Fatou K. [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Huyvaert, Marlene [Auteur]
178275|||Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)] (VALID)
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Ortalli, Ana [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Canouil, Mickaël [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Lecoeur, Cecile [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Verbanck, Marie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Lobbens, Stéphane [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Khamis, Amna [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Marselli, Lorella [Auteur]
Marchetti, Piero [Auteur]
Pattou Kerr-Conte, Julie [Auteur]
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Pattou, Francois [Auteur]
178275|||Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)] (VALID)
Marre, Michel [Auteur]
Université Sorbonne Paris Cité [USPC]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Roussel, Ronan [Auteur]
Centre de Recherche des Cordeliers [CRC (UMR_S_1138 / U1138)]
Université Sorbonne Paris Cité [USPC]
Balkau, Beverley [Auteur]
Université Paris-Saclay
Froguel, Philippe [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]
Bonnefond, Amelie [Auteur]
Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199
Metabolic functional (epi)genomics and molecular mechanisms involved in type 2 diabetes and related diseases - UMR 8199 - UMR 1283 [EGENODIA (GI3M)]

Journal title :

International Journal of Obesity

Abbreviated title :

Int J Obes (Lond)

Volume number :

44

Pages :

539–543

Publication date :

2019-08-06

ISSN :

1476-5497

HAL domain(s) :

Sciences du Vivant [q-bio]

English abstract : [en]

Background Genome-wide association studies (GWAS) have identified more than 250 loci associated with body mass index (BMI) and obesity. However, post-GWAS functional genomic investigations have been inadequate for ...
Show more >Background Genome-wide association studies (GWAS) have identified more than 250 loci associated with body mass index (BMI) and obesity. However, post-GWAS functional genomic investigations have been inadequate for understanding how these genetic loci physiologically impact disease development. Methods We performed a PCR-free expression assay targeting genes located nearby the GWAS-identified SNPs associated with BMI/obesity in a large panel of human tissues. Furthermore, we analyzed several genetic risk scores (GRS) summing GWAS-identified alleles associated with increased BMI in 4236 individuals. Results We found that the expression of BMI/obesity susceptibility genes was strongly enriched in the brain, especially in the insula (p = 4.7 × 10–9) and substantia nigra (p = 6.8 × 10–7), which are two brain regions involved in addiction and reward. Inversely, we found that top obesity/BMI-associated loci, including FTO, showed the strongest gene expression enrichment in the two brain regions. Conclusions Our data suggest for the first time that the susceptibility genes for common obesity may have an effect on eating addiction and reward behaviors through their high expression in substantia nigra and insula, i.e., a different pattern from monogenic obesity genes that act in the hypothalamus and cause hyperphagia. Further epidemiological studies with relevant food behavior phenotypes are necessary to confirm these findings.Show less >

Language :

Anglais

Audience :

Internationale

Popular science :

Non

Administrative institution(s) :

Université de Lille
Inserm
CHU Lille

Collections :

• Génomique Intégrative et Modélisation des Maladies Métaboliques (EGID) - UMR 8199

Submission date :

2024-01-19T23:46:22Z
2024-09-23T15:01:55Z
2024-09-23T15:05:51Z