Plasma apolipoprotein E levels and risk of dementia: A Mendelian randomization study of 106,562 individuals

TY - JOUR

T1 - Plasma apolipoprotein E levels and risk of dementia

T2 - A Mendelian randomization study of 106,562 individuals

AU - Rasmussen, Katrine L

AU - Tybjærg-Hansen, Anne

AU - Nordestgaard, Børge G

AU - Frikke-Schmidt, Ruth

N1 - Copyright © 2017. Published by Elsevier Inc.

PY - 2018/1

Y1 - 2018/1

N2 - Introduction In recent prospective studies, low plasma levels of apolipoprotein E (apoE) are associated with high risk of dementia. Whether this reflects a causal association remains to be established. Methods Using a Mendelian randomization approach, we studied 106,562 and 75,260 individuals from the general population in observational and genetic analyses, respectively. Results In observational analyses risk of Alzheimer's disease and all dementia increased stepwise as a function of stepwise lower apoE levels (P for trend, 2 × 10 −17 and 9 × 10 −21 ). APOE-weighted allele scores were associated with stepwise decreases in apoE (P for trend, <1 × 10 −300 ). In instrumental variable analysis, the causal risk ratios for a 1 mg/dL genetically determined lower apoE were 1.41 (1.27–1.57) for Alzheimer's disease and 1.33 (1.25–1.43) for all dementia (F-statistics = 3821). Discussion Genetic and hence lifelong low apoE is associated with high risk of dementia in the general population. The concordance between observational and genetic estimates suggests a potential causal relationship.

AB - Introduction In recent prospective studies, low plasma levels of apolipoprotein E (apoE) are associated with high risk of dementia. Whether this reflects a causal association remains to be established. Methods Using a Mendelian randomization approach, we studied 106,562 and 75,260 individuals from the general population in observational and genetic analyses, respectively. Results In observational analyses risk of Alzheimer's disease and all dementia increased stepwise as a function of stepwise lower apoE levels (P for trend, 2 × 10 −17 and 9 × 10 −21 ). APOE-weighted allele scores were associated with stepwise decreases in apoE (P for trend, <1 × 10 −300 ). In instrumental variable analysis, the causal risk ratios for a 1 mg/dL genetically determined lower apoE were 1.41 (1.27–1.57) for Alzheimer's disease and 1.33 (1.25–1.43) for all dementia (F-statistics = 3821). Discussion Genetic and hence lifelong low apoE is associated with high risk of dementia in the general population. The concordance between observational and genetic estimates suggests a potential causal relationship.

KW - Journal Article

U2 - 10.1016/j.jalz.2017.05.006

DO - 10.1016/j.jalz.2017.05.006

M3 - Journal article

C2 - 28774656

SN - 1552-5260

VL - 14

SP - 71

EP - 80

JO - Alzheimer's & Dementia

JF - Alzheimer's & Dementia

IS - 1

ER -