The expression of genes in top obesity-associated loci is enriched in insula and substantia nigra brain regions involved in addiction and reward.
Int J Obes (Lond)
; 44(2): 539-543, 2020 02.
Article
em En
| MEDLINE
| ID: mdl-31388097
ABSTRACT
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.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Recompensa
/
Substância Negra
/
Córtex Cerebral
/
Comportamento Aditivo
/
Obesidade
Tipo de estudo:
Prognostic_studies
/
Risk_factors_studies
Limite:
Adult
/
Humans
/
Middle aged
Idioma:
En
Revista:
Int J Obes (Lond)
Assunto da revista:
METABOLISMO
Ano de publicação:
2020
Tipo de documento:
Article
País de afiliação:
França