| 1. |
- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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| 2. |
- Björck, Svante, et al.
(författare)
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A South Atlantic island record uncovers shifts in westerlies and hydroclimate during the last glacial
- 2019
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Ingår i: Climate of the Past. - : Copernicus GmbH. - 1814-9324 .- 1814-9332. ; 15:6, s. 1939-1958
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Tidskriftsartikel (refereegranskat)abstract
- Changes in the latitudinal position and strength of the Southern Hemisphere westerlies (SHW) are thought to be tightly coupled to important climate processes, such as cross-equatorial heat fluxes, Atlantic Meridional Overturning Circulation (AMOC), the bipolar seesaw, Southern Ocean ventilation and atmospheric CO2 levels. However, many uncertainties regarding magnitude, direction, and causes and effects of past SHW shifts still exist due to lack of suitable sites and scarcity of information on SHW dynamics, especially from the last glacial. Here we present a detailed hydroclimate multiproxy record from a 36.4-18.6 kyr old lake sediment sequence on Nightingale Island (NI). It is strategically located at 37ĝF S in the central South Atlantic (SA) within the SHW belt and situated just north of the marine Subtropical Front (SF). This has enabled us to assess hydroclimate changes and their link to the regional climate development as well as to large-scale climate events in polar ice cores. The NI record exhibits a continuous impact of the SHW, recording shifts in both position and strength, and between 36 and 31 ka the westerlies show high latitudinal and strength-wise variability possibly linked to the bipolar seesaw. This was followed by 4 kyr of slightly falling temperatures, decreasing humidity and fairly southerly westerlies. After 27 ka temperatures decreased 3-4 ĝC, marking the largest hydroclimate change with drier conditions and a variable SHW position. We note that periods with more intense and southerly-positioned SHW seem to be related to periods of increased CO2 outgassing from the ocean, while changes in the cross-equatorial gradient during large northern temperature changes appear as the driving mechanism for the SHW shifts. Together with coeval shifts of the South Pacific westerlies, our results show that most of the Southern Hemisphere experienced simultaneous atmospheric circulation changes during the latter part of the last glacial. Finally we can conclude that multiproxy lake records from oceanic islands have the potential to record atmospheric variability coupled to large-scale climate shifts over vast oceanic areas..
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| 3. |
- Lin, HY, et al.
(författare)
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KLK3 SNP-SNP interactions for prediction of prostate cancer aggressiveness
- 2021
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Ingår i: Scientific reports. - : Springer Science and Business Media LLC. - 2045-2322. ; 11:1, s. 9264-
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Tidskriftsartikel (refereegranskat)abstract
- Risk classification for prostate cancer (PCa) aggressiveness and underlying mechanisms remain inadequate. Interactions between single nucleotide polymorphisms (SNPs) may provide a solution to fill these gaps. To identify SNP–SNP interactions in the four pathways (the angiogenesis-, mitochondria-, miRNA-, and androgen metabolism-related pathways) associated with PCa aggressiveness, we tested 8587 SNPs for 20,729 cases from the PCa consortium. We identified 3 KLK3 SNPs, and 1083 (P < 3.5 × 10–9) and 3145 (P < 1 × 10–5) SNP–SNP interaction pairs significantly associated with PCa aggressiveness. These SNP pairs associated with PCa aggressiveness were more significant than each of their constituent SNP individual effects. The majority (98.6%) of the 3145 pairs involved KLK3. The 3 most common gene–gene interactions were KLK3-COL4A1:COL4A2, KLK3-CDH13, and KLK3-TGFBR3. Predictions from the SNP interaction-based polygenic risk score based on 24 SNP pairs are promising. The prevalence of PCa aggressiveness was 49.8%, 21.9%, and 7.0% for the PCa cases from our cohort with the top 1%, middle 50%, and bottom 1% risk profiles. Potential biological functions of the identified KLK3 SNP–SNP interactions were supported by gene expression and protein–protein interaction results. Our findings suggest KLK3 SNP interactions may play an important role in PCa aggressiveness.
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| 4. |
- Callac, Nolwenn, et al.
(författare)
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Modes of carbon fixation in an arsenic and CO2-rich shallow hydrothermal ecosystem
- 2017
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Ingår i: Scientific Reports. - : Springer Science and Business Media LLC. - 2045-2322.
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Tidskriftsartikel (refereegranskat)abstract
- The seafloor sediments of Spathi Bay, Milos Island, Greece, are part of the largest arsenic-CO2-rich shallow submarine hydrothermal ecosystem on Earth. Here, white and brown deposits cap chemically distinct sediments with varying hydrothermal influence. All sediments contain abundant genes for autotrophic carbon fixation used in the Calvin-Benson-Bassham (CBB) and reverse tricaboxylic acid (rTCA) cycles. Both forms of RuBisCO, together with ATP citrate lyase genes in the rTCA cycle, increase with distance from the active hydrothermal centres and decrease with sediment depth. Clustering of RuBisCO Form II with a highly prevalent Zetaproteobacteria 16S rRNA gene density infers that iron-oxidizing bacteria contribute significantly to the sediment CBB cycle gene content. Three clusters form from different microbial guilds, each one encompassing one gene involved in CO2 fixation, aside from sulfate reduction. Our study suggests that the microbially mediated CBB cycle drives carbon fixation in the Spathi Bay sediments that are characterized by diffuse hydrothermal activity, high CO2, As emissions and chemically reduced fluids. This study highlights the breadth of conditions influencing the biogeochemistry in shallow CO2-rich hydrothermal systems and the importance of coupling highly specific process indicators to elucidate the complexity of carbon cycling in these ecosystems.
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| 5. |
- Chabangborn, Akkaneewut, et al.
(författare)
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Climate in Sundaland and Asian monsoon variability during the last deglaciation
- 2018
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Ingår i: Quaternary International. - : Elsevier BV. - 1040-6182 .- 1873-4553. ; 479, s. 141-147
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Tidskriftsartikel (refereegranskat)abstract
- The lack of semi-quantitative paleo data from mainland Southeast Asia, especially from the emergent Sundaland, creates a marked difficulty in following the past Asian monsoon variability. The published pollen records from the adjacent sites to the Sundaland were selected in this study and evaluated for the relationship between taxa and plant functional types (PFTs), and subsequently between PFTs and biome, to eventually reconstruct the semi-quantitative temporal temperature and precipitation profile. In order to comprehend the Asian monsoon modification between 18.5 and 11 ka BP, the derived pollen based temperature and precipitation records were further analyzed together with other selected speleothem records from the Asian monsoon region, with reference to the Greenland and Antarctic ice cores. The warmer temperature in the Southern Hemisphere caused a southward shift of the mean position of the Intertropical Convergent Zone (ITCZ) and weakened the summer monsoon in the Asian monsoon region between 18.5 and 15 ka BP. The Northern Hemisphere temperature played an important role in the Asian monsoon modification between 15 and 13.5 ka BP, where the warmer Northern Hemisphere conditions strengthened the summer monsoon intensity in the Asian monsoon region and moved the mean position of the ITCZ to the north. However, the opposing precipitation pattern between the East and the West Indian Ocean suggested the potential influence of the Walker circulation on the Sundaland climate from 13.5 to 11 ka BP.
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| 6. |
- Katrantsiotis, Christos, et al.
(författare)
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Eastern Mediterranean hydroclimate reconstruction over the last 3600 years based on sedimentary n-alkanes, their carbon and hydrogen isotope composition and XRF data from the Gialova Lagoon, SW Greece
- 2018
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Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 194, s. 77-93
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Tidskriftsartikel (refereegranskat)abstract
- Understanding past hydroclimate variability and related drivers is essential to improve climate forecasting capabilities especially in areas with high climatic sensitivity, such as the Mediterranean. This can be achieved by using a broad spectrum of high resolution, multiple proxy records which can also allow us to assess linkages between regional hydroclimate variability and shifts in the large-scale atmospheric patterns. Here, we present a multiproxy reconstruction of the central-eastern Mediterranean hydro climate changes over the last 3600 years based on a sediment core from the Gialova Lagoon, a shallow coastal ecosystem in SW Peloponnese, Greece. Our combined dataset consists of the distribution and compound-specific carbon and hydrogen isotope (delta C-13 and 8D) composition of n-alkanes, bulk organic matter properties and X-ray fluorescence (XRF) core scanning data. This approach was complemented with a semi-quantitative analysis of plant remains in the core. The results indicate a high contribution of local aquatic vegetation to organic matter. Large delta C-13 variations in predominantly aquatic plant-derived mid-chain alkanes (C23-23) mainly reflect changes in the aquatic plant abundance and their carbon source. Our data suggest that higher delta C-13(23-25) values (up to 19 parts per thousand) largely correspond to expansion of aquatic vegetation during wet and/or cold periods causing carbon-limiting conditions in the water and assimilation of isotopically-enriched bicarbonate by the plants. The 8D records of the individual n-alkanes (C-17 to C-31) exhibit a nearly identical pattern to each other, which implies that they all reflect changes in the source water isotope composition, driven by hydroclimate variability. In addition, the 8D profiles are consistent with the XRF data with both proxies being driven by a common hydroclimate signal. We observe two major shifts from dry and/or warm periods at ca 3600-3000 cal BP and ca 17001300 cal BP to wet and/or cold episodes at ca 3000-2700 cal BP and ca 1300-900 cal BP. The period ca 700-200 cal BP is the wettest and/or coldest in our record and coeval with the Little Ice Age. The climatic fluctuation reported in this study can be explained by the relative dominance of high-latitude (e.g. North Atlantic Oscillation during winters) and the low-latitude atmospheric patterns (Intertropical convergence zone, Subtropical High and the effects of Asian monsoons during summers) which suggests an Atlantic-Mediterranean-Monsoon climate link in this area for the late Holocene.
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