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- Bellenguez, C, et al.
(author)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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In: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Journal article (peer-reviewed)abstract
- Characterization of the genetic landscape of Alzheimer’s disease (AD) and related dementias (ADD) provides a unique opportunity for a better understanding of the associated pathophysiological processes. We performed a two-stage genome-wide association study totaling 111,326 clinically diagnosed/‘proxy’ AD cases and 677,663 controls. We found 75 risk loci, of which 42 were new at the time of analysis. Pathway enrichment analyses confirmed the involvement of amyloid/tau pathways and highlighted microglia implication. Gene prioritization in the new loci identified 31 genes that were suggestive of new genetically associated processes, including the tumor necrosis factor alpha pathway through the linear ubiquitin chain assembly complex. We also built a new genetic risk score associated with the risk of future AD/dementia or progression from mild cognitive impairment to AD/dementia. The improvement in prediction led to a 1.6- to 1.9-fold increase in AD risk from the lowest to the highest decile, in addition to effects of age and the APOE ε4 allele.
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- Sim, HW, et al.
(author)
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Beta-blockers and renin-angiotensin system inhibitors in acute myocardial infarction managed with inhospital coronary revascularization
- 2020
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In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 15184-
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Journal article (peer-reviewed)abstract
- Pivotal trials of beta-blockers (BB) and angiotensin converting enzyme inhibitors/angiotensin receptor blockers (ACEI/ARB) in acute myocardial infarction (AMI) were largely conducted prior to the widespread adoption of early revascularization. A total of 15,073 patients with AMI who underwent inhospital coronary revascularization from January 2007 to December 2013 were analyzed. At 12 months, BB was significantly associated with a lower incidence of major adverse cardiovascular events (MACE, adjusted HR 0.80, 95% CI 0.70–0.93) and all-cause mortality (adjusted HR 0.69, 95% CI 0.55–0.88), while ACEI/ARB was significantly associated with lower all-cause mortality (adjusted HR 0.80, 95% CI 0.66–0.98) and heart failure (HF) hospitalization (adjusted HR 0.80, 95% CI 0.68–0.95). Combined BB and ACEI/ARB use was associated with the lowest incidence of MACE (adjusted HR 0.70, 95% CI 0.57–0.86), all-cause mortality (adjusted HR 0.55, 95% CI 0.40–0.77) and HF hospitalization (adjusted HR 0.64, 95% CI 0.48–0.86). This were consistent for left ventricular ejection fraction < 50% or ≥ 50%. In conclusion, in AMI managed with revascularization, both BB and ACEI/ARB were associated with a lower incidence of 12-month all-cause mortality. Combined BB and ACEI/ARB was associated with the lowest incidence of all-cause mortality and HF hospitalization.
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