title: FTO, obesity and the adolescent brain.
abstract: 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.
authors.affiliation: The Hospital for Sick Children, University of Toronto, Toronto, Canada.
authors.forename: Melkaye G
authors.initials: MG
authors.lastname: Melka
authors.forename: Jesse
authors.initials: J
authors.lastname: Gillis
authors.forename: Manon
authors.initials: M
authors.lastname: Bernard
authors.forename: Michal
authors.initials: M
authors.lastname: Abrahamowicz
authors.forename: M Mallar
authors.initials: MM
authors.lastname: Chakravarty
authors.forename: Gabriel T
authors.initials: GT
authors.lastname: Leonard
authors.forename: Michel
authors.initials: M
authors.lastname: Perron
authors.forename: Louis
authors.initials: L
authors.lastname: Richer
authors.forename: Suzanne
authors.initials: S
authors.lastname: Veillette
authors.forename: Tobias
authors.initials: T
authors.lastname: Banaschewski
authors.forename: Gareth J
authors.initials: GJ
authors.lastname: Barker
authors.forename: Christian
authors.initials: C
authors.lastname: Büchel
authors.forename: Patricia
authors.initials: P
authors.lastname: Conrod
authors.forename: Herta
authors.initials: H
authors.lastname: Flor
authors.forename: Andreas
authors.initials: A
authors.lastname: Heinz
authors.forename: Hugh
authors.initials: H
authors.lastname: Garavan
authors.forename: Rüdiger
authors.initials: R
authors.lastname: Brühl
authors.forename: Karl
authors.initials: K
authors.lastname: Mann
authors.forename: Eric
authors.initials: E
authors.lastname: Artiges
authors.forename: Anbarasu
authors.initials: A
authors.lastname: Lourdusamy
authors.forename: Mark
authors.initials: M
authors.lastname: Lathrop
authors.forename: Eva
authors.initials: E
authors.lastname: Loth
authors.forename: Yannick
authors.initials: Y
authors.lastname: Schwartz
authors.forename: Vincent
authors.initials: V
authors.lastname: Frouin
authors.forename: Marcella
authors.initials: M
authors.lastname: Rietschel
authors.forename: Michael N
authors.initials: MN
authors.lastname: Smolka
authors.forename: Andreas
authors.initials: A
authors.lastname: Ströhle
authors.forename: Jürgen
authors.initials: J
authors.lastname: Gallinat
authors.forename: Maren
authors.initials: M
authors.lastname: Struve
authors.forename: Eva
authors.initials: E
authors.lastname: Lattka
authors.forename: Melanie
authors.initials: M
authors.lastname: Waldenberger
authors.forename: Gunter
authors.initials: G
authors.lastname: Schumann
authors.forename: Paul
authors.initials: P
authors.lastname: Pavlidis
authors.forename: Daniel
authors.initials: D
authors.lastname: Gaudet
authors.forename: Tomás
authors.initials: T
authors.lastname: Paus
authors.forename: Zdenka
authors.initials: Z
authors.lastname: Pausova
mesh_terms: D000273:Adipose Tissue / Q000378:metabolism; D050154:Adiposity / Q000235:genetics; D000293:Adolescent; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000886:Anthropometry; D015992:Body Mass Index; D001921:Brain / Q000033:anatomy & histology* / Q000378:metabolism; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D009765:Obesity / Q000235:genetics* / Q000378:metabolism; D011506:Proteins / Q000235:genetics* / Q000378:metabolism
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human