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

doi: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

Research output: Contribution to journal › Article › peer-review

25 Scopus citations

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	https://doi.org/10.1016/j.jalz.2015.05.015
State	Published - 1 Dec 2015

Keywords

Alzheimer's disease
Dementia
Mendelian randomization
Obesity

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10.1016/j.jalz.2015.05.015

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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, 11(12), 1439-1451. https://doi.org/10.1016/j.jalz.2015.05.015

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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'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",

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doi = "10.1016/j.jalz.2015.05.015",

language = "English",

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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 journal › Article › 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 C.

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

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U2 - 10.1016/j.jalz.2015.05.015

DO - 10.1016/j.jalz.2015.05.015

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AN - SCOPUS:84952308113

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JO - Alzheimer's and Dementia

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SN - 1552-5260

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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