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 language | English |
|---|---|
| Pages (from-to) | 1439-1451 |
| Number of pages | 13 |
| Journal | Alzheimer's and Dementia |
| Volume | 11 |
| Issue number | 12 |
| DOIs | |
| State | Published - 1 Dec 2015 |
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Keywords
- Alzheimer's disease
- Dementia
- Mendelian randomization
- Obesity
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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 journal › Article › Research › peer-review
TY - JOUR
T1 - Genetically predicted body mass index and Alzheimer's disease-related phenotypes in three large samples
T2 - Mendelian randomization analyses
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.
AU - Asthana, Sanjay
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
Y1 - 2015/12/1
N2 - 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.
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
UR - http://www.scopus.com/inward/record.url?scp=84952308113&partnerID=8YFLogxK
U2 - 10.1016/j.jalz.2015.05.015
DO - 10.1016/j.jalz.2015.05.015
M3 - Article
VL - 11
SP - 1439
EP - 1451
JO - Alzheimer's and Dementia
JF - Alzheimer's and Dementia
SN - 1552-5260
IS - 12
ER -