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Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses.

TitleGenetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses.
Publication TypeJournal Article
Year of Publication2015
AuthorsMukherjee, S, Walter, S, Kauwe, JSK, Saykin, AJ, Bennett, DA, Larson, EB, Crane, PK, M Glymour, M
Corporate AuthorsAdult Changes in Thought Study Investigators, Religious Orders Study/Memory and Aging Project Investigators, Alzheimer's Disease Genetics Consortium
JournalAlzheimers Dement
Volume11
Issue12
Pagination1439-1451
Date Published2015 Dec
ISSN1552-5279
KeywordsAged, Aged, 80 and over, Alzheimer Disease, Body Mass Index, Female, Genotype, Humans, Linear Models, Male, Mendelian Randomization Analysis, Obesity, Phenotype, Polymorphism, Single Nucleotide, Risk Factors
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.

DOI10.1016/j.jalz.2015.05.015
Alternate JournalAlzheimers Dement
PubMed ID26079416
PubMed Central IDPMC4676945
Grant ListP30 AG013854 / AG / NIA NIH HHS / United States
MH60451 / MH / NIMH NIH HHS / United States
RC4 AG039029 / AG / NIA NIH HHS / United States
RC4AG039029 / AG / NIA NIH HHS / United States
UL1 TR001445 / TR / NCATS NIH HHS / United States
R01 AG054060 / AG / NIA NIH HHS / United States
P30 AG010124 / AG / NIA NIH HHS / United States
P50 AG023501 / AG / NIA NIH HHS / United States
R01 AG17917 / AG / NIA NIH HHS / United States
U01 HG006375 / HG / NHGRI NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
AG041232 / AG / NIA NIH HHS / United States
R01 AG019771 / AG / NIA NIH HHS / United States
P30 AG028377 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
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P30 AG10133 / AG / NIA NIH HHS / United States
R01 AG035137 / AG / NIA NIH HHS / United States
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U01 AG024904 / AG / NIA NIH HHS / United States
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UL1 RR029893 / RR / NCRR NIH HHS / United States
/ / Medical Research Council / United Kingdom
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AG05128 / AG / NIA NIH HHS / United States
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AG019757 / AG / NIA NIH HHS / United States
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IK2 BX001820 / BX / BLRD VA / United States
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