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- Jones, Lesley, et al.
(författare)
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Convergent genetic and expression data implicate immunity in Alzheimer's disease
- 2015
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Ingår i: Alzheimer's & Dementia. - : Wiley. - 1552-5260 .- 1552-5279. ; 11:6, s. 658-671
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Tidskriftsartikel (refereegranskat)abstract
- Background: Late-onset Alzheimer's disease (AD) is heritable with 20 genes showing genome-wide association in the International Genomics of Alzheimer's Project (IGAP). To identify the biology underlying the disease, we extended these genetic data in a pathway analysis. Methods: The ALIGATOR and GSEA algorithms were used in the IGAP data to identify associated functional pathways and correlated gene expression networks in human brain. Results: ALIGATOR identified an excess of curated biological pathways showing enrichment of association. Enriched areas of biology included the immune response (P = 3.27 X 10(-12) after multiple testing correction for pathways), regulation of endocytosis (P = 1.31 X 10(-11)), cholesterol transport (P = 2.96 X 10(-9)), and proteasome-ubiquitin activity (P = 1.34 X 10(-6)). Correlated gene expression analysis identified four significant network modules, all related to the immune response (corrected P = .002-.05). Conclusions: The immime response, regulation of endocytosis, cholesterol transport, and protein ubiquitination represent prime targets for AD therapeutics.
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| 2. |
- White, Richard A., et al.
(författare)
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Does suicide have a stronger association with seasonality than sunlight?
- 2015
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Ingår i: BMJ Open. - : BMJ. - 2044-6055. ; 5:6
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Tidskriftsartikel (refereegranskat)abstract
- Objectives: Suicide rates have widely been reported to peak in spring and summer. A frequent hypothesis is that increased sunlight exposure alters biological mechanisms. However, few attempts have been made to systematically untangle the putative suicidogenic risk of sunlight exposure from that of seasonality. We examined whether average hours of daily sunlight in a month confer additional risk over month of year when predicting monthly suicide rates. Design: Historical population-based ecological longitudinal study. Setting and participants: We used 3 longitudinal studies (n=31 060 suicides) with monthly suicide and meteorological data from Greece (1992-2001), Victoria, Australia (1990-1998) and Norway (1969-2009). Intervention: We used a negative binomial regression to observe (1) the association of month of year with suicides, adjusting for different sunlight exposures, and (2) the association of sunlight exposure with suicides, adjusting for month of year. We then investigated claims that suicides were associated with daily sunlight exposures, defined by us as 2550 sunlight exposure combinations corresponding to a 1-50 days exposure window with lags of 0-50 days. Results: Using monthly data, the association between month of year and suicides remained after adjusting for mean daily hours of sunlight and change in the mean daily hours of sunlight. Adjusted for month of year, the associations between sunlight exposure and suicides became non-significant and attenuated towards the null (the coefficient estimate for mean daily hours of sunlight decreased in absolute magnitude by 72%). The findings were consistent across all 3 cohorts, both when analysed separately and combined. When investigating daily sunlight exposures, we found no significant results after correcting for multiple testing. Conclusions: Using monthly data, the robustness of our month of year effects, combined with the transient and modest nature of our sunlight effects, suggested that the association between sunlight exposure and suicide was a proxy for the association between seasonality and suicide.
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