Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples

Mendelian randomization analyses

Adult Changes in Thought Study Investigators, Religious Orders Study/Memory and Aging Project Investigators, Alzheimer's Disease Genetics Consortium

Research output: Contribution to journalArticleResearchpeer-review

15 Citations (Scopus)

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.

Original languageEnglish
Pages (from-to)1439-1451
Number of pages13
JournalAlzheimer's and Dementia
Volume11
Issue number12
DOIs
StatePublished - 1 Dec 2015

Fingerprint

Mendelian Randomization Analysis
Alzheimer Disease
Body Mass Index
Phenotype
Odds Ratio
Retirement
Random Allocation
Causality
Single Nucleotide Polymorphism
Dementia
Confidence Intervals

Keywords

  • Alzheimer's disease
  • Dementia
  • Mendelian randomization
  • Obesity

Cite this

Adult Changes in Thought Study Investigators, Religious Orders Study/Memory and Aging Project Investigators, & Alzheimer's Disease Genetics Consortium (2015). Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses. Alzheimer's and Dementia, 11(12), 1439-1451. https://doi.org/10.1016/j.jalz.2015.05.015
Adult Changes in Thought Study Investigators ; Religious Orders Study/Memory and Aging Project Investigators ; Alzheimer's Disease Genetics Consortium. / Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples : Mendelian randomization analyses. In: Alzheimer's and Dementia. 2015 ; Vol. 11, No. 12. pp. 1439-1451.
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Adult Changes in Thought Study Investigators, Religious Orders Study/Memory and Aging Project Investigators & Alzheimer's Disease Genetics Consortium 2015, 'Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses', Alzheimer's and Dementia, vol. 11, no. 12, pp. 1439-1451. https://doi.org/10.1016/j.jalz.2015.05.015

Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples : Mendelian randomization analyses. / Adult Changes in Thought Study Investigators; Religious Orders Study/Memory and Aging Project Investigators; Alzheimer's Disease Genetics Consortium.

In: Alzheimer's and Dementia, Vol. 11, No. 12, 01.12.2015, p. 1439-1451.

Research output: Contribution to journalArticleResearchpeer-review

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AU - Adult Changes in Thought Study Investigators

AU - Religious Orders Study/Memory and Aging Project Investigators

AU - Alzheimer's Disease Genetics Consortium

AU - Mukherjee, Shubhabrata

AU - Walter, Stefan

AU - Kauwe, John S.K.

AU - Saykin, Andrew J.

AU - Bennett, David A.

AU - Larson, Eric B.

AU - Crane, Paul K.

AU - Glymour, M. Maria

AU - Albert, Marilyn S.

AU - Albin, Roger L.

AU - Apostolova, Liana G.

AU - Arnold, Steven E.

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AU - Atwood, Craig S.

AU - Baldwin, Clinton T.

AU - Barber, Robert Clinton

AU - Barmada, Michael M.

AU - Barnes, Lisa L.

AU - Beach, Thomas G.

AU - Becker, James T.

AU - Beecham, Gary W.

AU - Beekly, Duane

AU - Bigio, Eileen H.

AU - Bird, Thomas D.

AU - Blacker, Deborah

AU - Boeve, Bradley F.

AU - Bowen, James D.

AU - Boxer, Adam

AU - Burke, James R.

AU - Buxbaum, Joseph D.

AU - Cairns, Nigel J.

AU - Cantwell, Laura B.

AU - Cao, Chuanhai

AU - Carlson, Chris S.

AU - Carlsson, Cynthia M.

AU - Carney, Regina M.

AU - Carrasquillo, Minerva M.

AU - Carroll, Steven L.

AU - Chui, Helena C.

AU - Clark, David G.

AU - Corneveaux, Jason

AU - Cribbs, David H.

AU - Crocco, Elizabeth A.

AU - Cruchaga, Carlos

AU - De Jager, Philip L.

AU - DeCarli, Charles

AU - Demirci, F. Yesim

AU - Dick, Malcolm

AU - Dickson, Dennis W.

AU - Duara, Ranjan

PY - 2015/12/1

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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.

KW - Alzheimer's disease

KW - Dementia

KW - Mendelian randomization

KW - Obesity

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Adult Changes in Thought Study Investigators, Religious Orders Study/Memory and Aging Project Investigators, Alzheimer's Disease Genetics Consortium. Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples: Mendelian randomization analyses. Alzheimer's and Dementia. 2015 Dec 1;11(12):1439-1451. https://doi.org/10.1016/j.jalz.2015.05.015