1. |
- Wightman, D. P., et al.
(author)
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A genome-wide association study with 1,126,563 individuals identifies new risk loci for Alzheimer’s disease
- 2021
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In: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:9, s. 1276-1282
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Journal article (peer-reviewed)abstract
- Late-onset Alzheimer’s disease is a prevalent age-related polygenic disease that accounts for 50–70% of dementia cases. Currently, only a fraction of the genetic variants underlying Alzheimer’s disease have been identified. Here we show that increased sample sizes allowed identification of seven previously unidentified genetic loci contributing to Alzheimer’s disease. This study highlights microglia, immune cells and protein catabolism as relevant to late-onset Alzheimer’s disease, while identifying and prioritizing previously unidentified genes of potential interest. We anticipate that these results can be included in larger meta-analyses of Alzheimer’s disease to identify further genetic variants that contribute to Alzheimer’s pathology.
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2. |
- Savage, J. E., et al.
(author)
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Genome-wide association meta-analysis in 269,867 individuals identifies new genetic and functional links to intelligence
- 2018
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:7, s. 912-919
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Journal article (peer-reviewed)abstract
- Intelligence is highly heritable 1 and a major determinant of human health and well-being 2 . Recent genome-wide meta-analyses have identified 24 genomic loci linked to variation in intelligence 3-7, but much about its genetic underpinnings remains to be discovered. Here, we present a large-scale genetic association study of intelligence (n = 269,867), identifying 205 associated genomic loci (190 new) and 1,016 genes (939 new) via positional mapping, expression quantitative trait locus (eQTL) mapping, chromatin interaction mapping, and gene-based association analysis. We find enrichment of genetic effects in conserved and coding regions and associations with 146 nonsynonymous exonic variants. Associated genes are strongly expressed in the brain, specifically in striatal medium spiny neurons and hippocampal pyramidal neurons. Gene set analyses implicate pathways related to nervous system development and synaptic structure. We confirm previous strong genetic correlations with multiple health-related outcomes, and Mendelian randomization analysis results suggest protective effects of intelligence for Alzheimer's disease and ADHD and bidirectional causation with pleiotropic effects for schizophrenia. These results are a major step forward in understanding the neurobiology of cognitive function as well as genetically related neurological and psychiatric disorders.
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3. |
- Jansen, I. E., et al.
(author)
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Genome-wide meta-analysis identifies new loci and functional pathways influencing Alzheimer’s disease risk
- 2019
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In: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:3, s. 404-413
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Journal article (peer-reviewed)abstract
- Alzheimer’s disease (AD) is highly heritable and recent studies have identified over 20 disease-associated genomic loci. Yet these only explain a small proportion of the genetic variance, indicating that undiscovered loci remain. Here, we performed a large genome-wide association study of clinically diagnosed AD and AD-by-proxy (71,880 cases, 383,378 controls). AD-by-proxy, based on parental diagnoses, showed strong genetic correlation with AD (rg = 0.81). Meta-analysis identified 29 risk loci, implicating 215 potential causative genes. Associated genes are strongly expressed in immune-related tissues and cell types (spleen, liver, and microglia). Gene-set analyses indicate biological mechanisms involved in lipid-related processes and degradation of amyloid precursor proteins. We show strong genetic correlations with multiple health-related outcomes, and Mendelian randomization results suggest a protective effect of cognitive ability on AD risk. These results are a step forward in identifying the genetic factors that contribute to AD risk and add novel insights into the neurobiology of AD.
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4. |
- Persson, P., et al.
(author)
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Self-propagating high-temperature synthesis and liquid-phase sintering of TiC/Fe composites
- 2002
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In: Journal of Materials Processing Technology. - 0924-0136 .- 1873-4774. ; 127:2, s. 131-139
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Journal article (peer-reviewed)abstract
- The present paper addresses a possible route for the manufacturing of iron-based metal-matrix composites (MMCs) with a high level of reinforcement. The ceramic reinforcement studied was titanium carbide (TiC). TiC is one of the hardest materials to be found, which is why a TiC/Fe composite has the potential to be used as armour. Two manufacturing routes have been evaluated experimentally, i.e., liquid-phase sintering (LPS) and self-propagating high-temperature synthesis (SHS). LPS was found to be more effective due to easier process control and due to the process yielding a more homogeneous material. Both LPS and SHS produced a material with a relatively high degree of porosity. The porosity in the LPS experiments could be decreased by varying the process parameters, but this was not possible in the SHS process. Metallographic investigation shows that the TiC/Fe system is feasible and that applications utilising TiC/Fe composites are possible in the future. This is due to the fact that despite the porosity, an improvement of the MMC properties is detected, compared to those of the matrix material. © 2002 Elsevier Science B.V. All rights reserved.
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