@article{65a275446aec4aeaa7ddf080125dea04,
title = "Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses",
abstract = "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.",
keywords = "Alzheimer's disease, Dementia, Mendelian randomization, Obesity",
author = "{Adult Changes in Thought Study Investigators} and {Religious Orders Study/Memory and Aging Project Investigators} and {Alzheimer{\textquoteright}s Disease Genetics Consortium} and Shubhabrata Mukherjee and Stefan Walter and Kauwe, {John S.K.} and Saykin, {Andrew J.} and Bennett, {David A.} and Larson, {Eric B.} and Crane, {Paul K.} and Glymour, {M. Maria} and Albert, {Marilyn S.} and Albin, {Roger L.} and Apostolova, {Liana G.} and Arnold, {Steven E.} and Sanjay Asthana and Atwood, {Craig S.} and Baldwin, {Clinton T.} and Barber, {Robert C.} and Barmada, {Michael M.} and Barnes, {Lisa L.} and Beach, {Thomas G.} and Becker, {James T.} and Beecham, {Gary W.} and Duane Beekly and Bigio, {Eileen H.} and Bird, {Thomas D.} and Deborah Blacker and Boeve, {Bradley F.} and Bowen, {James D.} and Adam Boxer and Burke, {James R.} and Buxbaum, {Joseph D.} and Cairns, {Nigel J.} and Cantwell, {Laura B.} and Chuanhai Cao and Carlson, {Chris S.} and Carlsson, {Cynthia M.} and Carney, {Regina M.} and Carrasquillo, {Minerva M.} and Carroll, {Steven L.} and Chui, {Helena C.} and Clark, {David G.} and Jason Corneveaux and Cribbs, {David H.} and Crocco, {Elizabeth A.} and Carlos Cruchaga and {De Jager}, {Philip L.} and Charles DeCarli and Demirci, {F. Yesim} and Malcolm Dick and Dickson, {Dennis W.} and Ranjan Duara",
note = "Funding Information: ACT: ACT is supported by a grant ( U01 AG 06781 , to E.B.L. and P.K.C.) from the National Institutes of Health . Funding Information: ROS/MAP: ROS and MAP are supported by National Institute on Aging grants R01AG17917 , R01AG34374 , R01AG15819 , and P30AG10161 (all to D.A.B.). Funding Information: The Health and Retirement Study genetic data are sponsored by the National Institute on Aging (grant numbers U01AG009740 , RC2AG036495 , and RC4AG039029 ) and was conducted by the University of Michigan. Publisher Copyright: {\textcopyright} 2015 The Alzheimer's Association.",
year = "2015",
month = dec,
day = "1",
doi = "10.1016/j.jalz.2015.05.015",
language = "English",
volume = "11",
pages = "1439--1451",
journal = "Alzheimer's and Dementia",
issn = "1552-5260",
publisher = "Elsevier Inc.",
number = "12",
}