| 1. |
- Kanai, M, et al.
(författare)
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- 2023
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swepub:Mat__t
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| 2. |
- Niemi, MEK, et al.
(författare)
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- 2021
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swepub:Mat__t
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| 3. |
- Fernandez-Rozadilla, Ceres, et al.
(författare)
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Deciphering colorectal cancer genetics through multi-omic analysis of 100,204 cases and 154,587 controls of European and east Asian ancestries
- 2023
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 55, s. 89-99
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Tidskriftsartikel (refereegranskat)abstract
- Colorectal cancer (CRC) is a leading cause of mortality worldwide. We conducted a genome-wide association study meta-analysis of 100,204 CRC cases and 154,587 controls of European and east Asian ancestry, identifying 205 independent risk associations, of which 50 were unreported. We performed integrative genomic, transcriptomic and methylomic analyses across large bowel mucosa and other tissues. Transcriptome- and methylome-wide association studies revealed an additional 53 risk associations. We identified 155 high-confidence effector genes functionally linked to CRC risk, many of which had no previously established role in CRC. These have multiple different functions and specifically indicate that variation in normal colorectal homeostasis, proliferation, cell adhesion, migration, immunity and microbial interactions determines CRC risk. Crosstissue analyses indicated that over a third of effector genes most probably act outside the colonic mucosa. Our findings provide insights into colorectal oncogenesis and highlight potential targets across tissues for new CRC treatment and chemoprevention strategies.
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| 4. |
- Chen, Zhishan, et al.
(författare)
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Fine-mapping analysis including over 254 000 East Asian and European descendants identifies 136 putative colorectal cancer susceptibility genes
- 2024
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Ingår i: Nature Communications. - : Springer Nature. - 2041-1723. ; 15:1
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies (GWAS) have identified more than 200 common genetic variants independently associated with colorectal cancer (CRC) risk, but the causal variants and target genes are mostly unknown. We sought to fine-map all known CRC risk loci using GWAS data from 100,204 cases and 154,587 controls of East Asian and European ancestry. Our stepwise conditional analyses revealed 238 independent association signals of CRC risk, each with a set of credible causal variants (CCVs), of which 28 signals had a single CCV. Our cis-eQTL/mQTL and colocalization analyses using colorectal tissue-specific transcriptome and methylome data separately from 1299 and 321 individuals, along with functional genomic investigation, uncovered 136 putative CRC susceptibility genes, including 56 genes not previously reported. Analyses of single-cell RNA-seq data from colorectal tissues revealed 17 putative CRC susceptibility genes with distinct expression patterns in specific cell types. Analyses of whole exome sequencing data provided additional support for several target genes identified in this study as CRC susceptibility genes. Enrichment analyses of the 136 genes uncover pathways not previously linked to CRC risk. Our study substantially expanded association signals for CRC and provided additional insight into the biological mechanisms underlying CRC development.
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| 5. |
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| 6. |
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| 7. |
- Huyghe, Jeroen R., et al.
(författare)
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Discovery of common and rare genetic risk variants for colorectal cancer
- 2019
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 51:1, s. 76-
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Tidskriftsartikel (refereegranskat)abstract
- To further dissect the genetic architecture of colorectal cancer (CRC), we performed whole-genome sequencing of 1,439 cases and 720 controls, imputed discovered sequence variants and Haplotype Reference Consortium panel variants into genome-wide association study data, and tested for association in 34,869 cases and 29,051 controls. Findings were followed up in an additional 23,262 cases and 38,296 controls. We discovered a strongly protective 0.3% frequency variant signal at CHD1. In a combined meta-analysis of 125,478 individuals, we identified 40 new independent signals at P < 5 x 10(-8), bringing the number of known independent signals for CRC to similar to 100. New signals implicate lower-frequency variants, Kruppel-like factors, Hedgehog signaling, Hippo-YAP signaling, long noncoding RNAs and somatic drivers, and support a role for immune function. Heritability analyses suggest that CRC risk is highly polygenic, and larger, more comprehensive studies enabling rare variant analysis will improve understanding of biology underlying this risk and influence personalized screening strategies and drug development.
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| 8. |
- Wayman, Joseph P., et al.
(författare)
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Assessing taxonomic and functional change in British breeding bird assemblages over time
- 2022
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Ingår i: Global Ecology and Biogeography. - : Wiley. - 1466-822X .- 1466-8238. ; 31:5, s. 925-939
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Tidskriftsartikel (refereegranskat)abstract
- Aim: The aim was to identify the primary drivers of compositional change in breeding bird assemblages over a 40-year period. Location: Britain. Time period: From 1970 to 2010. Major taxa studied: Birds. Methods: Using morphological trait measurements and a dataset of presence–absence data for British breeding birds surveyed in 10 km × 10 km hectads during two time periods, we calculated temporal taxonomic and functional beta diversity for each hectad alongside the change in species richness, mean nearest taxon distance (MNTD) and mean pairwise distance (MPD). We also estimated potential drivers of beta diversity, including climatic and land-use and land-cover (LULC) change variables, elevation and assemblage species richness in 1970 (1970rich). We used random forest regressions to test which variables best explained compositional change in the assemblages. We also assessed spatial taxonomic and functional change by analysing multiple-site beta diversity and pairwise dissimilarities between time periods. Results: Initial (1970) species richness was the most important predictor (highest importance score) across all models, with areas characterized by higher initial richness experiencing less assemblage change overall. The coordinates included to capture spatial autocorrelation in the data were also important predictors of change. Most climate and LULC variables had relatively low explanatory power; elevation and average temperature were the most influential. All metrics increased slightly with increasing elevation, except for species richness change and MPD, which decreased. Main conclusions: The composition of British breeding bird assemblages changed substantially between 1970 and 2010. Spatial heterogeneity increased, both taxonomically and functionally. We show evidence that hectads with larger assemblages have been buffered from temporal diversity change and that those at higher elevations changed more in composition than those at lower elevations. Overall, coarse-resolution climate and LULC explained only small to moderate amounts of variation, suggesting that stochastic assembly change or finer-scale drivers might be drivers of temporal changes in assemblage composition.
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| 9. |
- Wayman, Joseph P., et al.
(författare)
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Identifying the Drivers of Spatial Taxonomic and Functional Beta-Diversity of British Breeding Birds
- 2021
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Ingår i: Frontiers in Ecology and Evolution. - : Frontiers Media SA. - 2296-701X. ; 9
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Tidskriftsartikel (refereegranskat)abstract
- Spatial variation in community composition may be driven by a variety of processes, including environmental filtering and dispersal limitation. While work has been conducted on the relative importance of these processes on various taxa and at varying resolutions, tests using high-resolution empirical data across large spatial extents are sparse. Here, we use a dataset on the presence/absence of breeding bird species collected at the 10 km × 10 km scale across the whole of Britain. Pairwise spatial taxonomic and functional beta diversity, and the constituent components of each (turnover and nestedness/richness loss or gain), were calculated alongside two other measures of functional change (mean nearest taxon distance and mean pairwise distance). Predictor variables included climate and land use measures, as well as a measure of elevation, human influence, and habitat diversity. Generalized dissimilarity modeling was used to analyze the contribution of each predictor variable to variation in the different beta diversity metrics. Overall, we found that there was a moderate and unique proportion of the variance explained by geographical distance per se, which could highlight the role of dispersal limitation in community dissimilarity. Climate, land use, and human influence all also contributed to the observed patterns, but a large proportion of the explained variance in beta diversity was shared between these variables and geographical distance. However, both taxonomic nestedness and functional nestedness were uniquely predicted by a combination of land use, human influence, elevation, and climate variables, indicating a key role for environmental filtering. These findings may have important conservation implications in the face of a warming climate and future land use change.
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| 10. |
- Asuk, Sijeh A., et al.
(författare)
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Impact of human foraging on tree diversity, composition, and abundance in a tropical rainforest
- 2023
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Ingår i: Biotropica. - : Wiley. - 0006-3606 .- 1744-7429. ; 55:1, s. 232-245
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Tidskriftsartikel (refereegranskat)abstract
- Tropical forest tree communities are structured by a range of large-scale drivers including elevation, certain high-impact anthropogenic activities (e.g., deforestation), and fires. However, low-impact human activities such as foraging may also be subtly but notably altering the composition of tropical forest tree communities. The study assessed the (i) differences in species diversity, patterns of relative abundance, and pairwise beta diversity between trees with edible and inedible fruits and seeds along an elevation gradient, and (ii) impact of human foraging on the forest tree communities in Oban Division of Cross River National Park, Nigeria. Fifteen permanent 40 by 40 m plots were established along an elevational gradient (120–460 m above mean sea level). All trees of 0.1 m diameter at breast height (dbh) and above were measured, identified, and, with the aid of structured questionnaires, classified into those with edible and inedible fruits/seeds. A total of 35 edible species with density of 128 stems/hectare and basal area of 11.99 m2/hectare, and 109 inedible species with density of 364 stems/hectare and basal area of 22.42 m2/hectare were sampled. However, the evenness of edible and inedible species was similar at pooled and plot levels. For inedible species, there was a positive relationship between pairwise beta diversity and elevation, and this was driven mainly by turnover. In contrast, edible species exhibited a non-significant trend between elevation and beta diversity. Thus, the study showed that human foraging of edible fruits may have subtly influenced patterns of species diversity and community structure in this tropical forest.
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