Title | Alzheimer's disease genetic risk variants beyond APOE ε4 predict mortality |
Publication Type | Journal Article |
Year of Publication | 2017 |
Authors | Mez, 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 |
Journal | Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring |
Volume | 8 |
Pagination | 188-195 |
ISSN Number | 23528729 |
Keywords | Alzheimer'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. |
URL | http://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 |
DOI | 10.1016/j.dadm.2017.07.002 |
Short Title | Alzheimer's & Dementia: Diagnosis, Assessment & Disease Monitoring |
Citation Key | 9337 |
PubMed ID | 28983503 |
PubMed Central ID | PMC5604953 |
Grant List | K99 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 |