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
ISSN Number1552-5279
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
User Guide Notes

http://www.ncbi.nlm.nih.gov/pubmed/26079416?dopt=Abstract

Alternate JournalAlzheimers Dement
Citation Key10640
PubMed ID26079416
PubMed Central IDPMC4676945
Grant List5R01AG022374 / AG / NIA NIH HHS / United States
AG05144 / AG / NIA NIH HHS / United States
P30 AG013854 / AG / NIA NIH HHS / United States
RC4AG039029 / AG / NIA NIH HHS / United States
MH60451 / MH / NIMH NIH HHS / United States
RC4 AG039029 / 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
R01 AG019771 / AG / NIA NIH HHS / United States
P30 AG028377 / AG / NIA NIH HHS / United States
RC2 AG036528 / AG / NIA NIH HHS / United States
AG041232 / AG / NIA NIH HHS / United States
RF1 AG015819 / AG / NIA NIH HHS / United States
P50 AG008671 / AG / NIA NIH HHS / United States
P50 AG005142 / AG / NIA NIH HHS / United States
U01 AG10483 / AG / NIA NIH HHS / United States
P30 AG10133 / AG / NIA NIH HHS / United States
R01 AG035137 / AG / NIA NIH HHS / United States
P30 AG010133 / AG / NIA NIH HHS / United States
U24 AG021886 / AG / NIA NIH HHS / United States
R01 AG031581 / AG / NIA NIH HHS / United States
U01 AG009740 / AG / NIA NIH HHS / United States
P50 AG005131 / AG / NIA NIH HHS / United States
P50 AG016574 / AG / NIA NIH HHS / United States
P50 AG005146 / AG / NIA NIH HHS / United States
P50 AG016577 / AG / NIA NIH HHS / United States
R01 AG019085 / AG / NIA NIH HHS / United States
U01 AG032984 / AG / NIA NIH HHS / United States
R01 AG042611 / AG / NIA NIH HHS / United States
R01 AG013616 / AG / NIA NIH HHS / United States
R01 AG030146 / AG / NIA NIH HHS / United States
U01 AG024904 / AG / NIA NIH HHS / United States
P50 AG008702 / AG / NIA NIH HHS / United States
UL1 RR029893 / RR / NCRR NIH HHS / United States
/ CAPMC / CIHR / Canada
R01 AA023416 / AA / NIAAA NIH HHS / United States
/ HHMI / Howard Hughes Medical Institute / United States
AG05128 / AG / NIA NIH HHS / United States
U01 AG016976 / AG / NIA NIH HHS / United States
P50 NS039764 / NS / NINDS NIH HHS / United States
P01 AG003991 / AG / NIA NIH HHS / United States
P30 AG008051 / AG / NIA NIH HHS / United States
P50 AG005681 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
U24 AG056270 / AG / NIA NIH HHS / United States
RC2 AG036502 / AG / NIA NIH HHS / United States
R01 AG017917 / AG / NIA NIH HHS / United States
R01AG17917 / AG / NIA NIH HHS / United States
R01 MH080295 / MH / NIMH NIH HHS / United States
P01 AG03991 / AG / NIA NIH HHS / United States
U01 AG 06781 / AG / NIA NIH HHS / United States
P50 AG005136 / AG / NIA NIH HHS / United States
AG010491 / AG / NIA NIH HHS / United States
P30 AG08051 / AG / NIA NIH HHS / United States
P30 AG012300 / AG / NIA NIH HHS / United States
NS39764 / NS / NINDS NIH HHS / United States
UL1 TR001108 / TR / NCATS NIH HHS / United States
AG041718 / AG / NIA NIH HHS / United States
R01 AG012101 / AG / NIA NIH HHS / United States
P50 AG016573 / AG / NIA NIH HHS / United States
P01 AG019724 / AG / NIA NIH HHS / United States
P50 AG016570 / AG / NIA NIH HHS / United States
P30 AG008017 / AG / NIA NIH HHS / United States
R01 AG008122 / AG / NIA NIH HHS / United States
P50 AG005134 / AG / NIA NIH HHS / United States
P30 AG010161 / AG / NIA NIH HHS / United States
R01 AG033193 / AG / NIA NIH HHS / United States
1RC2AG036502 / AG / NIA NIH HHS / United States
AG030653 / AG / NIA NIH HHS / United States
R01 AG15819 / AG / NIA NIH HHS / United States
U24 AG026390 / AG / NIA NIH HHS / United States
AG025688 / AG / NIA NIH HHS / United States
/ MRC_ / Medical Research Council / United Kingdom
1R01 AG035137 / AG / NIA NIH HHS / United States
R37 AG015473 / AG / NIA NIH HHS / United States
U24 AG026395 / AG / NIA NIH HHS / United States
AG027944 / AG / NIA NIH HHS / United States
P50 AG025688 / AG / NIA NIH HHS / United States
R01 CA129769 / CA / NCI NIH HHS / United States
P50 AG005133 / AG / NIA NIH HHS / United States
U01 AG010483 / AG / NIA NIH HHS / United States
P01 AG002219 / AG / NIA NIH HHS / United States
R01AG15819 / AG / NIA NIH HHS / United States
U01 AG006781 / AG / NIA NIH HHS / United States
U01 AG06781 / AG / NIA NIH HHS / United States
R01 AG041797 / AG / NIA NIH HHS / United States
P50 AG005144 / AG / NIA NIH HHS / United States
P01 AG010491 / AG / NIA NIH HHS / United States
U01AG009740 / AG / NIA NIH HHS / United States
P50 AG005138 / AG / NIA NIH HHS / United States
R01 AG021547 / AG / NIA NIH HHS / United States
R01 AG041232 / AG / NIA NIH HHS / United States
R01 AG019757 / AG / NIA NIH HHS / United States
R01 AG020688 / AG / NIA NIH HHS / United States
R01 AG034374 / AG / NIA NIH HHS / United States
R43 AG051285 / AG / NIA NIH HHS / United States
5R01AG012101 / AG / NIA NIH HHS / United States
R01 AG030653 / AG / NIA NIH HHS / United States
R01 AG33193 / AG / NIA NIH HHS / United States
R01 AG027944 / AG / NIA NIH HHS / United States
R01 AG30146 / AG / NIA NIH HHS / United States
R01 AG017173 / AG / NIA NIH HHS / United States
R01 AG025259 / AG / NIA NIH HHS / United States
P30AG10161 / AG / NIA NIH HHS / United States
R01AG34374 / AG / NIA NIH HHS / United States
U01 HG004610 / HG / NHGRI NIH HHS / United States
RC2 AG036495 / AG / NIA NIH HHS / United States
P30 AG010129 / AG / NIA NIH HHS / United States
P30 AG019610 / AG / NIA NIH HHS / United States
P50 AG016582 / AG / NIA NIH HHS / United States
R01 AG041718 / AG / NIA NIH HHS / United States
5R01AG013616 / AG / NIA NIH HHS / United States
P50 AG016576 / AG / NIA NIH HHS / United States
P30 AG028383 / AG / NIA NIH HHS / United States
AG019757 / AG / NIA NIH HHS / United States
MO1RR00096 / RR / NCRR NIH HHS / United States
R01 AG026916 / AG / NIA NIH HHS / United States
RC2AG036495 / AG / NIA NIH HHS / United States
R01 NS059873 / NS / NINDS NIH HHS / United States
AG021547 / AG / NIA NIH HHS / United States
UL1RR02777 / RR / NCRR NIH HHS / United States
R01 AG015819 / AG / NIA NIH HHS / United States
IK2 BX001820 / BX / BLRD VA / United States
P50, P50 AG016575 / AG / NIA NIH HHS / United States