title: Fat mass and obesity gene and cognitive decline: the Atherosclerosis Risk in Communities Study.
abstract: OBJECTIVE
  To determine whether 4 genetic variants in the fat mass and obesity associated gene (FTO) identified in genome-wide association studies of diabetes and obesity are associated with cognitive change in midlife in the Atherosclerosis Risk in Communities (ARIC) Study.
  
  
  METHODS
  ARIC is a prospective cohort study of the development of atherosclerosis in 15,792 individuals aged 45 to 64 years at baseline from 1986 to 1989. FTO is highly expressed in human fetal and adult brain, and a single nucleotide polymorphism in FTO has previously been associated with reduced brain volume in cognitively normal subjects. Since a relationship between brain atrophy and diminished cognitive function has been demonstrated in ARIC participants, general linear models were used to evaluate the association between 6-year change in scores on 3 neuropsychological tests and FTO genotype.
  
  
  RESULTS
  In a sample of 8,364 white and 2,083 African American men and women with no clinical history of stroke, significantly greater mean change in performance on the Delayed Word Recall Test was associated with 2 of 4 FTO single nucleotide polymorphisms examined (rs9939609, rs805136, rs17817449, and rs1421085) in whites but not in African Americans (p ≤ 0.002). The association of the FTO polymorphisms with cognitive change was independent of potential confounding clinical and demographic variables including age, gender, education, diabetes, hypertension, and body mass index.
  
  
  CONCLUSIONS
  Further studies will be needed to clarify the biological mechanisms and genetic pathways through which variants in FTO can increase susceptibility to decline in verbal memory detectable in middle-aged, community-dwelling adults.
authors.affiliation: Human Genetics Center, School of Public Health, University of Texas Health Science Center at Houston, USA.
authors.forename: Jan
authors.initials: J
authors.lastname: Bressler
authors.forename: Myriam
authors.initials: M
authors.lastname: Fornage
authors.forename: Ellen W
authors.initials: EW
authors.lastname: Demerath
authors.forename: David S
authors.initials: DS
authors.lastname: Knopman
authors.forename: Keri L
authors.initials: KL
authors.lastname: Monda
authors.forename: Kari E
authors.initials: KE
authors.lastname: North
authors.forename: Alan
authors.initials: A
authors.lastname: Penman
authors.forename: Thomas H
authors.initials: TH
authors.lastname: Mosley
authors.forename: Eric
authors.initials: E
authors.lastname: Boerwinkle
mesh_terms: D001741:Black or African American / Q000235:genetics; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015992:Body Mass Index; D003072:Cognition Disorders / Q000235:genetics* / Q000523:psychology; D005260:Female; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology; D055106:Genome-Wide Association Study; D006801:Humans; D008297:Male; D008875:Middle Aged; D009483:Neuropsychological Tests / Q000706:statistics & numerical data; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011446:Prospective Studies; D011506:Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human