|Title||Fat mass and obesity gene and cognitive decline: the Atherosclerosis Risk in Communities Study.|
|Publication Type||Journal Article|
|Year of Publication||2013|
|Authors||Bressler J, Fornage M, Demerath EW, Knopman DS, Monda KL, North KE, Penman A, Mosley TH|
|Secondary Authors||Boerwinkle E|
|Date Published||2013 Jan 01|
|Keywords||African Americans, Alpha-Ketoglutarate-Dependent Dioxygenase FTO, Body Mass Index, Cognition Disorders, European Continental Ancestry Group, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Humans, Male, Middle Aged, Neuropsychological Tests, Polymorphism, Single Nucleotide, Prospective Studies, Proteins|
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.
|PubMed Central ID||PMC3589198|
|Grant List||U01 HL096812 / HL / NHLBI NIH HHS / United States |
HHSN268201100005C / HL / NHLBI NIH HHS / United States
HHSN268201100009C / HL / NHLBI NIH HHS / United States
HHSN268201100010C / HL / NHLBI NIH HHS / United States
HHSN268201100007C / HL / NHLBI NIH HHS / United States
HHSN268201100011C / HL / NHLBI NIH HHS / United States
HHSN268201100006C / HL / NHLBI NIH HHS / United States
HHSN268201100008C / HL / NHLBI NIH HHS / United States
HHSN268201100012C / HL / NHLBI NIH HHS / United States