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- Bellenguez, C, et al.
(författare)
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New insights into the genetic etiology of Alzheimer's disease and related dementias
- 2022
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 54:4, s. 412-436
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Tidskriftsartikel (refereegranskat)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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| 3. |
- Tedersoo, L., et al.
(författare)
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The Global Soil Mycobiome consortium dataset for boosting fungal diversity research
- 2021
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Ingår i: Fungal Diversity. - : Springer Science and Business Media LLC. - 1560-2745 .- 1878-9129. ; 111, s. 573-588
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Tidskriftsartikel (refereegranskat)abstract
- Fungi are highly important biotic components of terrestrial ecosystems, but we still have a very limited understanding about their diversity and distribution. This data article releases a global soil fungal dataset of the Global Soil Mycobiome consortium (GSMc) to boost further research in fungal diversity, biogeography and macroecology. The dataset comprises 722,682 fungal operational taxonomic units (OTUs) derived from PacBio sequencing of full-length ITS and 18S-V9 variable regions from 3200 plots in 108 countries on all continents. The plots are supplied with geographical and edaphic metadata. The OTUs are taxonomically and functionally assigned to guilds and other functional groups. The entire dataset has been corrected by excluding chimeras, index-switch artefacts and potential contamination. The dataset is more inclusive in terms of geographical breadth and phylogenetic diversity of fungi than previously published data. The GSMc dataset is available over the PlutoF repository.
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| 7. |
- Witoelar, A, et al.
(författare)
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Meta-analysis of Alzheimer's disease on 9,751 samples from Norway and IGAP study identifies four risk loci
- 2018
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 8:1, s. 18088-
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Tidskriftsartikel (refereegranskat)abstract
- A large fraction of genetic risk factors for Alzheimer’s Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed a meta-analysis using GWAS results from 2,893 AD cases and 6,858 cognitively normal controls from Norway and 25,580 cases and 48,466 controls from the International Genomics of Alzheimer’s Project (IGAP), denoted the discovery sample. Second, we selected the top hits (p < 1 × 10−6) from the discovery analysis for replication in an Icelandic cohort consisting of 5,341 cases and 110,008 controls. We identified a novel genomic region with genome-wide significant association with AD on chromosome 4 (combined analysis OR = 1.07, p = 2.48 x 10-8). This finding implicated HS3ST1, a gene expressed throughout the brain particularly in the cerebellar cortex. In addition, we identified IGHV1-68 in the discovery sample, previously not associated with AD. We also associated USP6NL/ECHDC3 and BZRAP1-AS1 to AD, confirming findings from a follow-up transethnic study. These new gene loci provide further evidence for AD as a polygenic disorder, and suggest new mechanistic pathways that warrant further investigation.
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| 8. |
- Epp, L. S., et al.
(författare)
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New environmental metabarcodes for analysing soil DNA: potential for studying past and present ecosystems
- 2012
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Ingår i: Molecular Ecology. - 0962-1083. ; 21:8, s. 1821-1833
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Tidskriftsartikel (refereegranskat)abstract
- Metabarcoding approaches use total and typically degraded DNA from environmental samples to analyse biotic assemblages and can potentially be carried out for any kinds of organisms in an ecosystem. These analyses rely on specific markers, here called metabarcodes, which should be optimized for taxonomic resolution, minimal bias in amplification of the target organism group and short sequence length. Using bioinformatic tools, we developed metabarcodes for several groups of organisms: fungi, bryophytes, enchytraeids, beetles and birds. The ability of these metabarcodes to amplify the target groups was systematically evaluated by (i) in silico PCRs using all standard sequences in the EMBL public database as templates, (ii) in vitro PCRs of DNA extracts from surface soil samples from a site in Varanger, northern Norway and (iii) in vitro PCRs of DNA extracts from permanently frozen sediment samples of late-Pleistocene age (similar to 16 00050 000 years bp) from two Siberian sites, Duvanny Yar and Main River. Comparison of the results from the in silico PCR with those obtained in vitro showed that the in silico approach offered a reliable estimate of the suitability of a marker. All target groups were detected in the environmental DNA, but we found large variation in the level of detection among the groups and between modern and ancient samples. Success rates for the Pleistocene samples were highest for fungal DNA, whereas bryophyte, beetle and bird sequences could also be retrieved, but to a much lesser degree. The metabarcoding approach has considerable potential for biodiversity screening of modern samples and also as a palaeoecological tool.
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| 9. |
- Fjell, A. M., et al.
(författare)
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Self-reported Sleep Problems Related to Amyloid Deposition in Cortical Regions with High HOMER1 Gene Expression
- 2020
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Ingår i: Cerebral Cortex. - : Oxford University Press (OUP). - 1047-3211 .- 1460-2199. ; 30:4, s. 2144-2156
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Tidskriftsartikel (refereegranskat)abstract
- Sleep problems are related to the elevated levels of the Alzheimer's disease (AD) biomarker beta-amyloid (AD) Hypotheses about the causes of this relationship can be generated from molecular markers of sleep problems identified in rodents. A major marker of sleep deprivation is Homerla, a neural protein coded by the HOMER1 gene, which has also been implicated in brain A beta accumulation. Here, we tested whether the relationship between cortical A beta accumulation and self-reported sleep quality, as well as changes in sleep quality over 3 years, was stronger in cortical regions with high HOMER1 mRNA expression levels. In a sample of 154 cognitively healthy older adults, A beta correlated with poorer sleep quality cross-sectionally and longitudinally (n = 62), but more strongly in the younger than in older individuals. Effects were mainly found in regions with high expression of HOMER1. The anatomical distribution of the sleep-A beta relationship followed closely the A beta accumulation pattern in 69 patients with mild cognitive impairment or AD. Thus, the results indicate that the relationship between sleep problems and A beta accumulation may involve Homer1 activity in the cortical regions, where harbor A beta deposits in AD. The findings may advance our understanding of the relationship between sleep problems and AD risk.
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