FTO, obesity and the adolescent brain

Published on Mar 1, 2013in Human Molecular Genetics4.54
· DOI :10.1093/hmg/dds504
Melkaye G. Melka5
Estimated H-index: 5
(U of T: University of Toronto),
Jesse Gillis23
Estimated H-index: 23
(UBC: University of British Columbia)
+ 33 AuthorsZdenka Pausova41
Estimated H-index: 41
(U of T: University of Toronto)
Genetic variations in fat mass- and obesity (FTO)-associated gene, a well-replicated gene locus of obesity, appear to be associated also with reduced regional brain volumes in elderly. Here, we examined whether FTO is associated with total brain volume in adolescence, thus exploring possible developmental effects of FTO. We studied a population-based sample of 598 adolescents recruited from the French Canadian founder population in whom we measured brain volume by magnetic resonance imaging. Total fat mass was assessed with bioimpedance and body mass index was determined with anthropometry. Genotype–phenotype associations were tested with Merlin under an additive model. We found that the G allele of FTO (rs9930333) was associated with higher total body fat [TBF (P = 0.002) and lower brain volume (P = 0.005)]. The same allele was also associated with higher lean body mass (P = 0.03) and no difference in height (P = 0.99). Principal component analysis identified a shared inverse variance between the brain volume and TBF, which was associated with FTO at P = 5.5 × 10−6. These results were replicated in two independent samples of 413 and 718 adolescents, and in a meta-analysis of all three samples (n = 1729 adolescents), FTO was associated with this shared inverse variance at P = 1.3 × 10−9. Co-expression networks analysis supported the possibility that the underlying FTO effects may occur during embryogenesis. In conclusion, FTO is associated with shared inverse variance between body adiposity and brain volume, suggesting that this gene may exert inverse effects on adipose and brain tissues. Given the completion of the overall brain growth in early childhood, these effects may have their origins during early development.
  • References (41)
  • Citations (35)
Jul 1, 2011 in ISMB (Intelligent Systems in Molecular Biology)
#1Jesse Gillis (UBC: University of British Columbia)H-Index: 23
#2Paul Pavlidis (UBC: University of British Columbia)H-Index: 52
#1Rachel Larder (University of Cambridge)H-Index: 10
#2M.K. Marcella Cheung (University of Cambridge)H-Index: 1
Last.Anthony P. Coll (University of Cambridge)H-Index: 28
view all 5 authors...
#1Xue Gao (BCM: Baylor College of Medicine)H-Index: 3
#2Yong Hyun Shin (BCM: Baylor College of Medicine)H-Index: 2
Last.Pumin Zhang (BCM: Baylor College of Medicine)H-Index: 35
view all 6 authors...
#1S.L. Zipursky (UCLA: University of California, Los Angeles)H-Index: 55
#2Joshua R. Sanes (Harvard University)H-Index: 118
Cited By35
#1Jiashuo Li (PRC: China Medical University (PRC))
#2Xinxin Yang (PRC: China Medical University (PRC))H-Index: 2
Last.Yu Deng (PRC: China Medical University (PRC))H-Index: 15
view all 9 authors...
#1Naser Kalantari (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 6
#2Nastaran Keshavarz Mohammadi (Shahid Beheshti University of Medical Sciences and Health Services)H-Index: 5
Last.Ghasem Azizi Tabesh (Tehran University of Medical Sciences)H-Index: 2
view all 10 authors...
#1Rajashekar Varma Kadumuri (IUPUI: Indiana University – Purdue University Indianapolis)H-Index: 1
#2Sarath Chandra Janga (IU: Indiana University)H-Index: 27
#1Theodora Sideratou (USYD: University of Sydney)
#2Fiona Atkinson (USYD: University of Sydney)H-Index: 16
Last.Jennie Brand-Miller (USYD: University of Sydney)H-Index: 50
view all 6 authors...
#1Margarita T. Angelova (CNRS: Centre national de la recherche scientifique)H-Index: 1
#2Dilyana G. Dimitrova (CNRS: Centre national de la recherche scientifique)H-Index: 1
Last.Jean-Yves RoignantH-Index: 12
view all 7 authors...
#1Freddy J. Alfaro (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 3
#2Anna Gavrieli (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 10
Last.NovakVera (BIDMC: Beth Israel Deaconess Medical Center)H-Index: 38
view all 6 authors...
View next paperN6-methyladenosine in nuclear RNA is a major substrate of the obesity-associated FTO.