| 1. |
- Kanai, M, et al.
(author)
-
- 2023
-
swepub:Mat__t
|
|
| 2. |
- Niemi, MEK, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 3. |
- Bravo, L, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 4. |
- Tabiri, S, et al.
(author)
-
- 2021
-
swepub:Mat__t
|
|
| 5. |
- Jiang, X., et al.
(author)
-
Shared heritability and functional enrichment across six solid cancers
- 2019
-
In: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10
-
Journal article (peer-reviewed)abstract
- Quantifying the genetic correlation between cancers can provide important insights into the mechanisms driving cancer etiology. Using genome-wide association study summary statistics across six cancer types based on a total of 296,215 cases and 301,319 controls of European ancestry, here we estimate the pair-wise genetic correlations between breast, colorectal, head/neck, lung, ovary and prostate cancer, and between cancers and 38 other diseases. We observed statistically significant genetic correlations between lung and head/neck cancer (r(g) = 0.57, p = 4.6 x 10(-8)), breast and ovarian cancer (r(g) = 0.24, p = 7 x 10(-5)), breast and lung cancer (r(g) = 0.18, p = 1.5 x 10(-6)) and breast and colorectal cancer (r(g) = 0.15, p = 1.1 x 10(-4)). We also found that multiple cancers are genetically correlated with non-cancer traits including smoking, psychiatric diseases and metabolic characteristics. Functional enrichment analysis revealed a significant excess contribution of conserved and regulatory regions to cancer heritability. Our comprehensive analysis of cross-cancer heritability suggests that solid tumors arising across tissues share in part a common germline genetic basis.
|
|
| 6. |
- Figlioli, G, et al.
(author)
-
The FANCM:p.Arg658* truncating variant is associated with risk of triple-negative breast cancer
- 2019
-
In: NPJ breast cancer. - : Springer Science and Business Media LLC. - 2374-4677. ; 5, s. 38-
-
Journal article (peer-reviewed)abstract
- Breast cancer is a common disease partially caused by genetic risk factors. Germline pathogenic variants in DNA repair genes BRCA1, BRCA2, PALB2, ATM, and CHEK2 are associated with breast cancer risk. FANCM, which encodes for a DNA translocase, has been proposed as a breast cancer predisposition gene, with greater effects for the ER-negative and triple-negative breast cancer (TNBC) subtypes. We tested the three recurrent protein-truncating variants FANCM:p.Arg658*, p.Gln1701*, and p.Arg1931* for association with breast cancer risk in 67,112 cases, 53,766 controls, and 26,662 carriers of pathogenic variants of BRCA1 or BRCA2. These three variants were also studied functionally by measuring survival and chromosome fragility in FANCM−/− patient-derived immortalized fibroblasts treated with diepoxybutane or olaparib. We observed that FANCM:p.Arg658* was associated with increased risk of ER-negative disease and TNBC (OR = 2.44, P = 0.034 and OR = 3.79; P = 0.009, respectively). In a country-restricted analysis, we confirmed the associations detected for FANCM:p.Arg658* and found that also FANCM:p.Arg1931* was associated with ER-negative breast cancer risk (OR = 1.96; P = 0.006). The functional results indicated that all three variants were deleterious affecting cell survival and chromosome stability with FANCM:p.Arg658* causing more severe phenotypes. In conclusion, we confirmed that the two rare FANCM deleterious variants p.Arg658* and p.Arg1931* are risk factors for ER-negative and TNBC subtypes. Overall our data suggest that the effect of truncating variants on breast cancer risk may depend on their position in the gene. Cell sensitivity to olaparib exposure, identifies a possible therapeutic option to treat FANCM-associated tumors.
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
- Kattge, Jens, et al.
(author)
-
TRY plant trait database - enhanced coverage and open access
- 2020
-
In: Global Change Biology. - : Wiley-Blackwell. - 1354-1013 .- 1365-2486. ; 26:1, s. 119-188
-
Journal article (peer-reviewed)abstract
- Plant traits-the morphological, anatomical, physiological, biochemical and phenological characteristics of plants-determine how plants respond to environmental factors, affect other trophic levels, and influence ecosystem properties and their benefits and detriments to people. Plant trait data thus represent the basis for a vast area of research spanning from evolutionary biology, community and functional ecology, to biodiversity conservation, ecosystem and landscape management, restoration, biogeography and earth system modelling. Since its foundation in 2007, the TRY database of plant traits has grown continuously. It now provides unprecedented data coverage under an open access data policy and is the main plant trait database used by the research community worldwide. Increasingly, the TRY database also supports new frontiers of trait-based plant research, including the identification of data gaps and the subsequent mobilization or measurement of new data. To support this development, in this article we evaluate the extent of the trait data compiled in TRY and analyse emerging patterns of data coverage and representativeness. Best species coverage is achieved for categorical traits-almost complete coverage for 'plant growth form'. However, most traits relevant for ecology and vegetation modelling are characterized by continuous intraspecific variation and trait-environmental relationships. These traits have to be measured on individual plants in their respective environment. Despite unprecedented data coverage, we observe a humbling lack of completeness and representativeness of these continuous traits in many aspects. We, therefore, conclude that reducing data gaps and biases in the TRY database remains a key challenge and requires a coordinated approach to data mobilization and trait measurements. This can only be achieved in collaboration with other initiatives.
|
|
| 11. |
|
|
| 12. |
- Orr, Russell J.S., et al.
(author)
-
Paleozoic origins of cheilostome bryozoans and their parental care inferred by a new genome-skimmed phylogeny
- 2022
-
In: Science Advances. - : American Association for the Advancement of Science (AAAS). - 2375-2548. ; 8:13
-
Journal article (peer-reviewed)abstract
- Phylogenetic relationships and the timing of evolutionary events are essential for understanding evolution on longer time scales. Cheilostome bryozoans are a group of ubiquitous, species-rich, marine colonial organisms with an excellent fossil record but lack phylogenetic relationships inferred from molecular data. We present genome-skimmed data for 395 cheilostomes and combine these with 315 published sequences to infer relationships and the timing of key events among c. 500 cheilostome species. We find that named cheilostome genera and species are phylogenetically coherent, rendering fossil or contemporary specimens readily delimited using only skeletal morphology. Our phylogeny shows that parental care in the form of brooding evolved several times independently but was never lost in cheilostomes. Our fossil calibration, robust to varied assumptions, indicates that the cheilostome lineage and parental care therein could have Paleozoic origins, much older than the first known fossil record of cheilostomes in the Late Jurassic.
|
|
| 13. |
- Chen, Hongjie, et al.
(author)
-
Large-scale cross-cancer fine-mapping of the 5p15.33 region reveals multiple independent signals
- 2021
-
In: Human Genetics and Genomics Advances. - : Cell Press. - 2666-2477. ; 2:3
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWASs) have identified thousands of cancer risk loci revealing many risk regions shared across multiple cancers. Characterizing the cross-cancer shared genetic basis can increase our understanding of global mechanisms of cancer development. In this study, we collected GWAS summary statistics based on up to 375,468 cancer cases and 530,521 controls for fourteen types of cancer, including breast (overall, estrogen receptor [ER]-positive, and ER-negative), colorectal, endometrial, esophageal, glioma, head/neck, lung, melanoma, ovarian, pancreatic, prostate, and renal cancer, to characterize the shared genetic basis of cancer risk. We identified thirteen pairs of cancers with statistically significant local genetic correlations across eight distinct genomic regions. Specifically, the 5p15.33 region, harboring the TERT and CLPTM1L genes, showed statistically significant local genetic correlations for multiple cancer pairs. We conducted a cross-cancer fine-mapping of the 5p15.33 region based on eight cancers that showed genome-wide significant associations in this region (ER-negative breast, colorectal, glioma, lung, melanoma, ovarian, pancreatic, and prostate cancer). We used an iterative analysis pipeline implementing a subset-based meta-analysis approach based on cancer-specific conditional analyses and identified ten independent cross-cancer associations within this region. For each signal, we conducted cross-cancer fine-mapping to prioritize the most plausible causal variants. Our findings provide a more in-depth understanding of the shared inherited basis across human cancers and expand our knowledge of the 5p15.33 region in carcinogenesis.
|
|
| 14. |
- Cheng, THT, et al.
(author)
-
Meta-analysis of genome-wide association studies identifies common susceptibility polymorphisms for colorectal and endometrial cancer near SH2B3 and TSHZ1
- 2015
-
In: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 5, s. 17369-
-
Journal article (peer-reviewed)abstract
- High-risk mutations in several genes predispose to both colorectal cancer (CRC) and endometrial cancer (EC). We therefore hypothesised that some lower-risk genetic variants might also predispose to both CRC and EC. Using CRC and EC genome-wide association series, totalling 13,265 cancer cases and 40,245 controls, we found that the protective allele [G] at one previously-identified CRC polymorphism, rs2736100 near TERT, was associated with EC risk (odds ratio (OR) = 1.08, P = 0.000167); this polymorphism influences the risk of several other cancers. A further CRC polymorphism near TERC also showed evidence of association with EC (OR = 0.92; P = 0.03). Overall, however, there was no good evidence that the set of CRC polymorphisms was associated with EC risk and neither of two previously-reported EC polymorphisms was associated with CRC risk. A combined analysis revealed one genome-wide significant polymorphism, rs3184504, on chromosome 12q24 (OR = 1.10, P = 7.23 × 10−9) with shared effects on CRC and EC risk. This polymorphism, a missense variant in the gene SH2B3, is also associated with haematological and autoimmune disorders, suggesting that it influences cancer risk through the immune response. Another polymorphism, rs12970291 near gene TSHZ1, was associated with both CRC and EC (OR = 1.26, P = 4.82 × 10−8), with the alleles showing opposite effects on the risks of the two cancers.
|
|
| 15. |
- Oddo, Dominic, et al.
(author)
-
Characterization of a Set of Small Planets with TESS and CHEOPS and an Analysis of Photometric Performance
- 2023
-
In: Astronomical Journal. - : American Astronomical Society. - 0004-6256 .- 1538-3881. ; 165:3
-
Journal article (peer-reviewed)abstract
- The radius valley carries implications for how the atmospheres of small planets form and evolve, but this feature is visible only with highly precise characterizations of many small planets. We present the characterization of nine planets and one planet candidate with both NASA TESS and ESA CHEOPS observations, which adds to the overall population of planets bordering the radius valley. While five of our planets—TOI 118 b, TOI 262 b, TOI 455 b, TOI 560 b, and TOI 562 b—have already been published, we vet and validate transit signals as planetary using follow-up observations for four new TESS planets, including TOI 198 b, TOI 244 b, TOI 444 b, and TOI 470 b. While a three times increase in primary mirror size should mean that one CHEOPS transit yields an equivalent model uncertainty in transit depth as about nine TESS transits in the case that the star is equally as bright in both bands, we find that our CHEOPS transits typically yield uncertainties equivalent to between two and 12 TESS transits, averaging 5.9 equivalent transits. Therefore, we find that while our fits to CHEOPS transits provide overall lower uncertainties on transit depth and better precision relative to fits to TESS transits, our uncertainties for these fits do not always match expected predictions given photon-limited noise. We find no correlations between number of equivalent transits and any physical parameters, indicating that this behavior is not strictly systematic, but rather might be due to other factors such as in-transit gaps during CHEOPS visits or nonhomogeneous detrending of CHEOPS light curves.
|
|
| 16. |
- Bolam, Kate A, et al.
(author)
-
The Osteogenic Effect of Impact-Loading and Resistance Exercise on Bone Mineral Density in Middle-Aged and Older Men : A Pilot Study.
- 2016
-
In: Gerontology. - : S. Karger AG. - 0304-324X .- 1423-0003. ; 62:1, s. 22-32
-
Journal article (peer-reviewed)abstract
- BACKGROUND: Regular exercise has been recommended as a potential strategy to counteract the age-related bone loss experienced by men; however, the optimal exercise prescription is not known.OBJECTIVE: To perform a pilot study to examine the osteogenic effect, safety and feasibility of a combined program of upper body resistance exercise and two doses of impact-loading exercise on bone mineral density (BMD) of middle-aged and older men.METHODS: Forty-two community-dwelling men aged 50-74 years were randomly assigned to either an exercise program of combined upper body resistance exercise and either high-dose impact-loading (HI; 80 jumps per session) or moderate-dose impact-loading (MOD; 40 jumps per session) or a control (CON) group. The 9-month intervention involved 4 sessions each week: 2 supervised clinic-based and 2 home-based. BMD of the lumbar spine, femoral neck, total hip, trochanter and whole body as well as lean and fat mass were assessed at baseline and 9 months by dual-energy X-ray absorptiometry. Bone turnover markers, hormone levels, physical function and muscle strength were also assessed.RESULTS: Following 9 months of training, significant differences in BMD among groups were found at the total hip (p = 0.010) and trochanter (p = 0.047) with BMD in the MOD group decreasing relative to the HI group. Although not significant, the HI group consistently preserved BMD, whereas BMD of the MOD and CON groups declined at the hip sites. Mean change for all groups at all skeletal sites was approximately within ±1%. There was no change in bone turnover markers. There were no adverse events as a result of the intervention; however, overall attendance for the HI and MOD groups was 53% (clinic: 68%, home: 38%) and 65% (clinic: 74%, home: 55%), respectively.CONCLUSIONS: This study indicates that while impact-loading exercise can be safely undertaken in middle-aged and older men, the current combined program did not elicit significant improvements in BMD. © 2015 S. Karger AG, Basel.
|
|
| 17. |
- Figtree, Gemma A., et al.
(author)
-
Clinical Pathway for Coronary Atherosclerosis in Patients Without Conventional Modifiable Risk Factors JACC State-of-the-Art Review
- 2023
-
In: Journal of the American College of Cardiology. - : ELSEVIER SCIENCE INC. - 0735-1097 .- 1558-3597. ; 82:13, s. 1343-1359
-
Research review (peer-reviewed)abstract
- Reducing the incidence and prevalence of standard modifiable cardiovascular risk factors (SMuRFs) is critical to tackling the global burden of coronary artery disease (CAD). However, a substantial number of individuals develop coronary atherosclerosis despite no SMuRFs. SMuRFless patients presenting with myocardial infarction have been observed to have an unexpected higher early mortality compared to their counterparts with at least 1 SMuRF. Evidence for optimal management of these patients is lacking. We assembled an international, multidisciplinary team to develop an evidence-based clinical pathway for SMuRFless CAD patients. A modified Delphi method was applied. The resulting pathway confirms underlying atherosclerosis and true SMuRFless status, ensures evidence-based secondary prevention, and considers additional tests and interventions for less typical contributors. This dedicated pathway for a previously overlooked CAD population, with an accompanying registry, aims to improve outcomes through enhanced adherence to evidence-based secondary prevention and additional diagnosis of modifiable risk factors observed. (c) 2023 The Authors. Published by Elsevier on behalf of the American College of Cardiology Foundation. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
|
|
| 18. |
- Lang, Daniel, et al.
(author)
-
The Physcomitrella patens chromosome-scale assembly reveals moss genome structure and evolution
- 2018
-
In: The Plant Journal. - : Wiley. - 0960-7412 .- 1365-313X. ; 93:3, s. 515-533
-
Journal article (peer-reviewed)abstract
- The draft genome of the moss model, Physcomitrella patens, comprised approximately 2000 unordered scaffolds. In order to enable analyses of genome structure and evolution we generated a chromosome-scale genome assembly using genetic linkage as well as (end) sequencing of long DNA fragments. We find that 57% of the genome comprises transposable elements (TEs), some of which may be actively transposing during the life cycle. Unlike in flowering plant genomes, gene-and TE-rich regions show an overall even distribution along the chromosomes. However, the chromosomes are mono-centric with peaks of a class of Copia elements potentially coinciding with centromeres. Gene body methylation is evident in 5.7% of the protein-coding genes, typically coinciding with low GC and low expression. Some giant virus insertions are transcriptionally active and might protect gametes from viral infection via siRNA mediated silencing. Structure-based detection methods show that the genome evolved via two rounds of whole genome duplications (WGDs), apparently common in mosses but not in liverworts and hornworts. Several hundred genes are present in colinear regions conserved since the last common ancestor of plants. These syntenic regions are enriched for functions related to plant-specific cell growth and tissue organization. The P. patens genome lacks the TE-rich pericentromeric and gene-rich distal regions typical for most flowering plant genomes. More non-seed plant genomes are needed to unravel how plant genomes evolve, and to understand whether the P. patens genome structure is typical for mosses or bryophytes.
|
|
| 19. |
- Lorenzen, Eline D., et al.
(author)
-
Species-specific responses of Late Quaternary megafauna to climate and humans
- 2011
-
In: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 479:7373, s. 359-364
-
Journal article (peer-reviewed)abstract
- Despite decades of research, the roles of climate and humans in driving the dramatic extinctions of large-bodied mammals during the Late Quaternary period remain contentious. Here we use ancient DNA, species distribution models and the human fossil record to elucidate how climate and humans shaped the demographic history of woolly rhinoceros, woolly mammoth, wild horse, reindeer, bison and musk ox. We show that climate has been a major driver of population change over the past 50,000 years. However, each species responds differently to the effects of climatic shifts, habitat redistribution and human encroachment. Although climate change alone can explain the extinction of some species, such as Eurasian musk ox and woolly rhinoceros, a combination of climatic and anthropogenic effects appears to be responsible for the extinction of others, including Eurasian steppe bison and wild horse. We find no genetic signature or any distinctive range dynamics distinguishing extinct from surviving species, emphasizing the challenges associated with predicting future responses of extant mammals to climate and human-mediated habitat change.
|
|
| 20. |
- Moharrek, Farideh, et al.
(author)
-
Diversification dynamics of cheilostome bryozoans based on a Bayesian analysis of the fossil record
- 2022
-
In: Palaeontology. - : Wiley. - 0031-0239 .- 1475-4983. ; 65:1
-
Journal article (peer-reviewed)abstract
- Cheilostomata is the most diverse and ecologically dominant order of bryozoans living today. We apply a Bayesian framework to estimate macroevolutionary rates of cheilostomes since the Late Jurassic across four datasets: (I) manually curated genus ranges; (II) published text-mined genus ranges; (III) non-revised Paleobiology Database (PBDB) records; (IV) revised and augmented PBDB records. All datasets revealed increased origination rates in the Albian, and a twin K–Pg and Danian extinction rate peak. High origination rates in the Late Selandian–Ypresian in Dataset I indicate the onset of an ascophoran-grade radiation. Lineage-through-time plots confirm the macroevolutionary lag preceding the radiation of cheilostomes in the middle Cretaceous, and their renewed diversification in the late Paleocene and Eocene. A multivariate birth–death model indicates that origination rates are shaped by diversity-dependent dynamics coupled with a positive correlation with sea surface temperature, while extinction rates negatively correlate with sea level. Text-mined data provide broadly similar rate dynamics as manually curated data, although discrepancies could be attributed to the omission of key literature in Dataset II, and the inclusion of new published and unpublished data, and revised ranges in Dataset I. Revision and augmentation of PBDB occurrences were necessary to generate rate profiles akin to those of Datasets I and II and highlight the risks of using unedited occurrence data. Our results support the widely held assumption that diversification dynamics are controlled by both biotic and abiotic factors, and pave the way for integrating fossils with molecular phylogenies to study these processes in more detail.
|
|
| 21. |
- Zhang, YD, et al.
(author)
-
Assessment of polygenic architecture and risk prediction based on common variants across fourteen cancers
- 2020
-
In: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1, s. 3353-
-
Journal article (peer-reviewed)abstract
- Genome-wide association studies (GWAS) have led to the identification of hundreds of susceptibility loci across cancers, but the impact of further studies remains uncertain. Here we analyse summary-level data from GWAS of European ancestry across fourteen cancer sites to estimate the number of common susceptibility variants (polygenicity) and underlying effect-size distribution. All cancers show a high degree of polygenicity, involving at a minimum of thousands of loci. We project that sample sizes required to explain 80% of GWAS heritability vary from 60,000 cases for testicular to over 1,000,000 cases for lung cancer. The maximum relative risk achievable for subjects at the 99th risk percentile of underlying polygenic risk scores (PRS), compared to average risk, ranges from 12 for testicular to 2.5 for ovarian cancer. We show that PRS have potential for risk stratification for cancers of breast, colon and prostate, but less so for others because of modest heritability and lower incidence.
|
|
