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

International Journal of Obesity : Journal of the International Association for the Study of Obesity
Fatou K NdiayeA Bonnefond

Abstract

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. 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. 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. 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...Continue Reading

References

Nov 15, 2001·Obesity Research·J E Blundell, A Gillett
Nov 7, 2008·Trends in Neurosciences·Nasir H Naqvi, Antoine Bechara
Mar 17, 2009·Science·Kareem A ZaghloulMichael J Kahana
Oct 12, 2010·Nature Genetics·Elizabeth K SpeliotesRuth J F Loos
Jun 29, 2011·BMC Medical Genomics·Hong JiaoIngrid Dahlman
Apr 10, 2012·Nature Genetics·Jonathan P BradfieldUNKNOWN Early Growth Genetics Consortium
Jan 24, 2014·The American Journal of Clinical Nutrition·Alan J FlintEric B Rimm
Sep 11, 2014·Neuroscience and Biobehavioral Reviews·Johannes HebebrandSuzanne L Dickson
Feb 13, 2015·Nature·Adam E LockeElizabeth K Speliotes
Jul 21, 2015·Obesity·Nadia MicaliDavid M Evans
Aug 20, 2015·The New England Journal of Medicine·Melina ClaussnitzerManolis Kellis
Jan 3, 2016·The American Journal of Pathology·Sarah X Luo, Eric J Huang

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Citations

Oct 8, 2020·Médecine sciences : M/S·Morgane BaronAmélie Bonnefond
Jul 29, 2021·Trends in Genetics : TIG·Melina Claussnitzer, Katalin Susztak
Sep 25, 2021·Nature Reviews. Genetics·Ruth J F Loos, Giles S H Yeo
Nov 5, 2021·The International Journal of Behavioral Nutrition and Physical Activity·Guiomar MasipUNKNOWN IDEFICS/I.Family Consortia

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Methods Mentioned

BETA
genotyping
fluorescence-activated cell sorting

Software Mentioned

SPSS

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