title: Genetic variants in the Fat and Obesity Associated (FTO) gene and risk of Alzheimer's disease.
abstract: BACKGROUND
  Recent studies showed that polymorphisms in the Fat and Obesity-Associated (FTO) gene have robust effects on obesity, obesity-related traits and endophenotypes associated with Alzheimer's disease (AD).
  
  
  METHODS
  We used 1,877 Caucasian cases and controls from the NIA-LOAD study and 1,093 Caribbean Hispanics to further explore the association of FTO with AD. Using logistic regression, we assessed 42 SNPs in introns 1 and 2, the region previously reported to be associated with AD endophenotypes, which had been derived by genome-wide screenings. In addition, we performed gene expression analyses of neuropathologically confirmed AD cases and controls of two independent datasets (19 AD cases, 10 controls; 176 AD cases, 188 controls) using within- and between-group factors ANOVA of log(10) transformed rank invariant normalized expression data.
  
  
  RESULTS
  In the NIALOAD study, one SNP was significantly associated with AD and three additional markers were close to significance (rs6499640, rs10852521, rs16945088, rs8044769, FDR p-value: 0.05<p<0.09). Two of the SNPs are in strong LD (D'>0.9) with the previously reported SNPs. In the Caribbean Hispanic dataset, we identified three SNPs (rs17219084, rs11075996, rs11075997, FDR p-value: 0.009<p<0.01) that were associated with AD. These results were confirmed by haplotype analyses and in a metaanalysis in which we included the ADNI dataset. FTO had a significantly lower expresssion in AD cases compared to controls in two independent datasets derived from human cortex and amygdala tissue, respectively (p = 2.18 × 10-5 and p<0.0001).
  
  
  CONCLUSIONS
  Our data support the notion that genetic variation in Introns 1 and 2 of the FTO gene may contribute to AD risk.
authors.affiliation: The Taub Institute for Research on Alzheimer's Disease and the Aging Brain, College of Physicians and Surgeons, Columbia University, New York, New York, United States of America.
authors.forename: Christiane
authors.initials: C
authors.lastname: Reitz
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Tosto
authors.forename: Richard
authors.initials: R
authors.lastname: Mayeux
authors.forename: Jose A
authors.initials: JA
authors.lastname: Luchsinger
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000483:Alleles; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D000544:Alzheimer Disease / Q000235:genetics*; D016022:Case-Control Studies; D058068:Endophenotypes; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006630:Hispanic or Latino / Q000235:genetics; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011506:Proteins / Q000235:genetics*; D044465:White People / Q000235:genetics
chemical_list: D011506:Proteins; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human