Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality

TitleAlzheimer's disease genetic risk variants beyond APOE ε4 predict mortality
Publication TypeJournal Article
Year of Publication2017
AuthorsMez, J, Marden, JR, Mukherjee, S, Walter, S, Gibbons, LE, Gross, AL, Zahodne, LB, Gilsanz, P, Brewster, P, Nho, K, Crane, PK, Larson, EB, M. Glymour, M
JournalAlzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Volume8
Pagination188-195
ISSN Number23528729
KeywordsAlzheimer's disease, APoE4, Cognitive Ability, Genetics, Mortality, Risk Factors
Abstract

We hypothesized that, like apolipoprotein E (APOE), other late-onset Alzheimer's disease (LOAD) genetic susceptibility loci predict mortality. Methods We used a weighted genetic risk score (GRS) from 21 non-APOE LOAD risk variants to predict survival in the Adult Changes in Thought and the Health and Retirement Studies. We meta-analyzed hazard ratios and examined models adjusted for cognitive performance or limited to participants with dementia. For replication, we assessed the GRS-longevity association in the Cohorts for Heart and Aging Research in Genomic Epidemiology, comparing cases surviving to age ≥90 years with controls who died between ages 55 and 80 years. Results Higher GRS predicted mortality (hazard ratio = 1.05; 95% confidence interval: 1.00–1.10, P =.04). After adjusting for cognitive performance or restricting to participants with dementia, the relationship was attenuated and no longer significant. In case-control analysis, the GRS was associated with reduced longevity (odds ratio = 0.64; 95% confidence interval: 0.41–1.00, P =.05). Discussion Non-APOE LOAD susceptibility loci confer risk for mortality, likely through effects on dementia incidence.

URLhttp://linkinghub.elsevier.com/retrieve/pii/S2352872917300416http://api.elsevier.com/content/article/PII:S2352872917300416?httpAccept=text/xmlhttp://api.elsevier.com/content/article/PII:S2352872917300416?httpAccept=text/plain
DOI10.1016/j.dadm.2017.07.002
Short TitleAlzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring
Citation Key9337
PubMed ID28983503
PubMed Central IDPMC5604953
Grant ListK99 AG047963 / AG / NIA NIH HHS / United States
R00 LM011384 / LM / NLM NIH HHS / United States
R03 AG054936 / AG / NIA NIH HHS / United States
P50 AG005146 / AG / NIA NIH HHS / United States
P30 AG013846 / AG / NIA NIH HHS / United States
P50 AG005136 / AG / NIA NIH HHS / United States
U01 AG006781 / AG / NIA NIH HHS / United States
K23 AG046377 / AG / NIA NIH HHS / United States
R01 LM012535 / LM / NLM NIH HHS / United States
T32 MH017119 / MH / NIMH NIH HHS / United States
F31 HL112613 / HL / NHLBI NIH HHS / United States
R13 AG030995 / AG / NIA NIH HHS / United States