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- Gao, YX, et al.
(författare)
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Mendelian randomization implies no direct causal association between leukocyte telomere length and amyotrophic lateral sclerosis
- 2020
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 10:1, s. 12184-
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Tidskriftsartikel (refereegranskat)abstract
- We employed Mendelian randomization (MR) to evaluate the causal relationship between leukocyte telomere length (LTL) and amyotrophic lateral sclerosis (ALS) with summary statistics from genome-wide association studies (n = ~ 38,000 for LTL and ~ 81,000 for ALS in the European population; n = ~ 23,000 for LTL and ~ 4,100 for ALS in the Asian population). We further evaluated mediation roles of lipids in the pathway from LTL to ALS. The odds ratio per standard deviation decrease of LTL on ALS was 1.10 (95% CI 0.93–1.31, p = 0.274) in the European population and 0.75 (95% CI 0.53–1.07, p = 0.116) in the Asian population. This null association was also detected between LTL and frontotemporal dementia in the European population. However, we found that an indirect effect of LTL on ALS might be mediated by low density lipoprotein (LDL) or total cholesterol (TC) in the European population. These results were robust against extensive sensitivity analyses. Overall, our MR study did not support the direct causal association between LTL and the ALS risk in neither population, but provided suggestive evidence for the mediation role of LDL or TC on the influence of LTL and ALS in the European population.
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- Bonham, LW, et al.
(författare)
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Genetic variation across RNA metabolism and cell death gene networks is implicated in the semantic variant of primary progressive aphasia
- 2019
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 9:1, s. 10854-
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Tidskriftsartikel (refereegranskat)abstract
- The semantic variant of primary progressive aphasia (svPPA) is a clinical syndrome characterized by neurodegeneration and progressive loss of semantic knowledge. Unlike many other forms of frontotemporal lobar degeneration (FTLD), svPPA has a highly consistent underlying pathology composed of TDP-43 (a regulator of RNA and DNA transcription metabolism). Previous genetic studies of svPPA are limited by small sample sizes and a paucity of common risk variants. Despite this, svPPA’s relatively homogenous clinicopathologic phenotype makes it an ideal investigative model to examine genetic processes that may drive neurodegenerative disease. In this study, we used GWAS metadata, tissue samples from pathologically confirmed frontotemporal lobar degeneration, and in silico techniques to identify and characterize protein interaction networks associated with svPPA risk. We identified 64 svPPA risk genes that interact at the protein level. The protein pathways represented in this svPPA gene network are critical regulators of RNA metabolism and cell death, such as SMAD proteins and NOTCH1. Many of the genes in this network are involved in TDP-43 metabolism. Contrary to the conventional notion that svPPA is a clinical syndrome with few genetic risk factors, our analyses show that svPPA risk is complex and polygenic in nature. Risk for svPPA is likely driven by multiple common variants in genes interacting with TDP-43, along with cell death,x` working in combination to promote neurodegeneration.
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| 5. |
- Ferrari, Raffaele, et al.
(författare)
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Frontotemporal dementia and its subtypes: a genome-wide association study.
- 2014
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Ingår i: Lancet Neurology. - 1474-4465. ; 13:7, s. 686-699
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Tidskriftsartikel (refereegranskat)abstract
- Frontotemporal dementia (FTD) is a complex disorder characterised by a broad range of clinical manifestations, differential pathological signatures, and genetic variability. Mutations in three genes-MAPT, GRN, and C9orf72-have been associated with FTD. We sought to identify novel genetic risk loci associated with the disorder.
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| 6. |
- Gallucci, M, et al.
(författare)
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Factors related to disability: Evidence from the "Treviso Longeva (TRELONG) Study"
- 2010
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Ingår i: Archives of gerontology and geriatrics. - : Elsevier BV. - 1872-6976 .- 0167-4943. ; 52:3, s. 309-16
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Tidskriftsartikel (refereegranskat)abstract
- Prolongation of life is an important public health goal as long as there is an emphasis on the quality of life (QoL) and independent living. Diminishing abilities to ambulate and participate in activities of daily living point to a serious decline in functional health, increasing the risk of institutionalization and death. In our work we found a pattern of factors associated with disability, especially cognitive impairment, as well as stroke, physical activity and performance, reading, and the nutritional biomarkers, blood albumin and high-density lipoprotein cholesterol (HDL-C). The attention to this cluster of markers, suggesting multidimensional prevention, may have unexpected good effects against disability.
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| 9. |
- Gustafson, Deborah, 1966, et al.
(författare)
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Body Mass Index, Cognition, Disability, APOE Genotype, and Mortality: The "Treviso Longeva" Study
- 2012
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Ingår i: American Journal of Geriatric Psychiatry. - 1064-7481. ; 20:7, s. 594-602
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: The concurrent contributions of dynamic, interrelated late-life parameters, such as bodymass index (BMI), cognition, and physical functioning on mortality in the elderly are unclear, as is the influence of APOE genotype. We explored these measures in relation to 7-year mortality in long-lived Italian elderly. Design: A representative, age-stratified, population sample. Setting: The Treviso Longeva (TRELONG) Study, in Treviso, Italy. Participants: Three hundred eleven men and 357 women, aged 70 years and older (mean age 84 +/- 8 years). Measurements: Seven-year mortality, BMI, Mini-Mental State Examination (MMSE) score, Activities of Daily Living (ADL), APOE genotype, and a variety of clinical and survey data. Results: In separate age-and sex-adjusted analyses, BMI <18.5 kg/m(2), MMSE <= 24, and ADL <6, were associated with greater 7-year mortality among adults aged 70 years and older. In a multivariate model including all factors, MMSE <= 24, and ADL <6 were associated with greater mortality; BMI >= 30 kg/m(2) was protective. There were no interactions between BMI, MMSE, or ADL. When excluding those dying within 3 years of baseline, only an MMSE <= 24 was related to mortality. APOE epsilon 4 was not related to mortality. Conclusion: Higher MMSE score, higher ADL score, and higher BMI, independent of age, sex, and other factors, are markers for longer life among northern Italian adults aged 70 years or older. Global cognition, BMI, and physical functioning, assessed by short, simple tests are profound indicators of death within less than a decade. (Am J Geriatr Psychiatry 2012; 20:594-602)
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