TY - JOUR T1 - Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses. JF - Alzheimers Dement Y1 - 2015 A1 - Mukherjee, Shubhabrata A1 - Stefan Walter A1 - Kauwe, John S K A1 - Andrew J Saykin A1 - David A Bennett A1 - Eric B Larson A1 - Paul K Crane A1 - M. Maria Glymour KW - Aged KW - Aged, 80 and over KW - Alzheimer disease KW - Body Mass Index KW - Female KW - Genotype KW - Humans KW - Linear Models KW - Male KW - Mendelian Randomization Analysis KW - Obesity KW - Phenotype KW - Polymorphism, Single Nucleotide KW - Risk Factors AB -

Observational research shows that higher body mass index (BMI) increases Alzheimer's disease (AD) risk, but it is unclear whether this association is causal. We applied genetic variants that predict BMI in Mendelian randomization analyses, an approach that is not biased by reverse causation or confounding, to evaluate whether higher BMI increases AD risk. We evaluated individual-level data from the AD Genetics Consortium (ADGC: 10,079 AD cases and 9613 controls), the Health and Retirement Study (HRS: 8403 participants with algorithm-predicted dementia status), and published associations from the Genetic and Environmental Risk for AD consortium (GERAD1: 3177 AD cases and 7277 controls). No evidence from individual single-nucleotide polymorphisms or polygenic scores indicated BMI increased AD risk. Mendelian randomization effect estimates per BMI point (95% confidence intervals) were as follows: ADGC, odds ratio (OR) = 0.95 (0.90-1.01); HRS, OR = 1.00 (0.75-1.32); GERAD1, OR = 0.96 (0.87-1.07). One subscore (cellular processes not otherwise specified) unexpectedly predicted lower AD risk.

VL - 11 IS - 12 U1 - http://www.ncbi.nlm.nih.gov/pubmed/26079416?dopt=Abstract ER -