| 1. |
|
|
| 2. |
- Craddock, Nick, et al.
(författare)
-
Genome-wide association study of CNVs in 16,000 cases of eight common diseases and 3,000 shared controls
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7289, s. 713-720
-
Tidskriftsartikel (refereegranskat)abstract
- Copy number variants (CNVs) account for a major proportion of human genetic polymorphism and have been predicted to have an important role in genetic susceptibility to common disease. To address this we undertook a large, direct genome-wide study of association between CNVs and eight common human diseases. Using a purpose-designed array we typed,19,000 individuals into distinct copy-number classes at 3,432 polymorphic CNVs, including an estimated similar to 50% of all common CNVs larger than 500 base pairs. We identified several biological artefacts that lead to false-positive associations, including systematic CNV differences between DNAs derived from blood and cell lines. Association testing and follow-up replication analyses confirmed three loci where CNVs were associated with disease-IRGM for Crohn's disease, HLA for Crohn's disease, rheumatoid arthritis and type 1 diabetes, and TSPAN8 for type 2 diabetes-although in each case the locus had previously been identified in single nucleotide polymorphism (SNP)-based studies, reflecting our observation that most common CNVs that are well-typed on our array are well tagged by SNPs and so have been indirectly explored through SNP studies. We conclude that common CNVs that can be typed on existing platforms are unlikely to contribute greatly to the genetic basis of common human diseases.
|
|
| 3. |
- Sawcer, Stephen, et al.
(författare)
-
Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
-
Tidskriftsartikel (refereegranskat)abstract
- Multiple sclerosis is a common disease of the central nervous system in which the interplay between inflammatory and neurodegenerative processes typically results in intermittent neurological disturbance followed by progressive accumulation of disability. Epidemiological studies have shown that genetic factors are primarily responsible for the substantially increased frequency of the disease seen in the relatives of affected individuals, and systematic attempts to identify linkage in multiplex families have confirmed that variation within the major histocompatibility complex (MHC) exerts the greatest individual effect on risk. Modestly powered genome-wide association studies (GWAS) have enabled more than 20 additional risk loci to be identified and have shown that multiple variants exerting modest individual effects have a key role in disease susceptibility. Most of the genetic architecture underlying susceptibility to the disease remains to be defined and is anticipated to require the analysis of sample sizes that are beyond the numbers currently available to individual research groups. In a collaborative GWAS involving 9,772 cases of European descent collected by 23 research groups working in 15 different countries, we have replicated almost all of the previously suggested associations and identified at least a further 29 novel susceptibility loci. Within the MHC we have refined the identity of the HLA-DRB1 risk alleles and confirmed that variation in the HLA-A gene underlies the independent protective effect attributable to the class I region. Immunologically relevant genes are significantly overrepresented among those mapping close to the identified loci and particularly implicate T-helper-cell differentiation in the pathogenesis of multiple sclerosis.
|
|
| 4. |
- Beecham, Ashley H, et al.
(författare)
-
Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
-
Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
-
Tidskriftsartikel (refereegranskat)abstract
- Using the ImmunoChip custom genotyping array, we analyzed 14,498 subjects with multiple sclerosis and 24,091 healthy controls for 161,311 autosomal variants and identified 135 potentially associated regions (P < 1.0 × 10(-4)). In a replication phase, we combined these data with previous genome-wide association study (GWAS) data from an independent 14,802 subjects with multiple sclerosis and 26,703 healthy controls. In these 80,094 individuals of European ancestry, we identified 48 new susceptibility variants (P < 5.0 × 10(-8)), 3 of which we found after conditioning on previously identified variants. Thus, there are now 110 established multiple sclerosis risk variants at 103 discrete loci outside of the major histocompatibility complex. With high-resolution Bayesian fine mapping, we identified five regions where one variant accounted for more than 50% of the posterior probability of association. This study enhances the catalog of multiple sclerosis risk variants and illustrates the value of fine mapping in the resolution of GWAS signals.
|
|
| 5. |
- Murawski, Christopher D., et al.
(författare)
-
Terminology for osteochondral lesions of the ankle: proceedings of the International Consensus Meeting on Cartilage Repair of the Ankle
- 2022
-
Ingår i: JOURNAL OF ISAKOS JOINT DISORDERS & ORTHOPAEDIC SPORTS MEDICINE. - : Elsevier BV. - 2059-7754 .- 2059-7762. ; 7:2, s. 62-66
-
Tidskriftsartikel (refereegranskat)abstract
- Background: The evidence supporting best practice guidelines in the field of cartilage repair of the ankle is based on both low quality and low levels of evidence. Therefore, an international consensus group of experts was convened to collaboratively advance toward consensus opinions based on the best available evidence on key topics within cartilage repair of the ankle. The purpose of this article is to report the consensus statements on "terminology for osteochondral lesions of the ankle" developed at the 2019 International Consensus Meeting on Cartilage Repair of the Ankle. Methods: Forty-three international experts in cartilage repair of the ankle representing 20 countries were convened and participated in a process based on the Delphi method of achieving consensus. Questions and statements were drafted within four working groups focusing on specific topics within cartilage repair of the ankle, after which a comprehensive literature review was performed, and the available evidence for each state-ment was graded. Discussion and debate occurred in cases where statements were not agreed on in unanimous fashion within the working groups. A final vote was then held, and the strength of consensus was characterised as follows: consensus, 51%-74%; strong consensus, 75%-99%; unanimous, 100%. Results: A total of 11 statements on terminology and classification reached consensus during the 2019 Interna-tional Consensus Meeting on Cartilage Repair of the Ankle. Definitions are provided for osseous, chondral and osteochondral lesions, as well as bone marrow stimulation and injury chronicity, among others. An osteochondral lesion of the talus can be abbreviated as OLT. Conclusions: This international consensus derived from leaders in the field will assist clinicians with the appro-priate terminology for osteochondral lesions of the ankle.
|
|
| 6. |
- Graham, Alastair G. C., et al.
(författare)
-
Seabed corrugations beneath an Antarctic ice shelf revealed by autonomous underwater vehicle survey : Origin and implications for the history of Pine Island Glacier
- 2013
-
Ingår i: Journal of Geophysical Research: Earth Surface. - : American Geophysical Union (AGU). - 2169-9011 .- 2169-9003. ; 118:3, s. 1356-1366
-
Tidskriftsartikel (refereegranskat)abstract
- [1] Ice shelves are critical features in the debate about West Antarctic ice sheet change and sea level rise, both because they limit ice discharge and because they are sensitive to change in the surrounding ocean. The Pine Island Glacier ice shelf has been thinning rapidly since at least the early 1990s, which has caused its trunk to accelerate and retreat. Although the ice shelf front has remained stable for the past six decades, past periods of ice shelf collapse have been inferred from relict seabed “corrugations” (corrugated ridges), preserved 340 km from the glacier in Pine Island Trough. Here we present high-resolution bathymetry gathered by an autonomous underwater vehicle operating beneath an Antarctic ice shelf, which provides evidence of long-term change in Pine Island Glacier. Corrugations and ploughmarks on a sub-ice shelf ridge that was a former grounding line closely resemble those observed offshore, interpreted previously as the result of iceberg grounding. The same interpretation here would indicate a significantly reduced ice shelf extent within the last 11 kyr, implying Holocene glacier retreat beyond present limits, or a past tidewater glacier regime different from today. The alternative, that corrugations were not formed in open water, would question ice shelf collapse events interpreted from the geological record, revealing detail of another bed-shaping process occurring at glacier margins. We assess hypotheses for corrugation formation and suggest periodic grounding of ice shelf keels during glacier unpinning as a viable origin. This interpretation requires neither loss of the ice shelf nor glacier retreat and is consistent with a “stable” grounding-line configuration throughout the Holocene.
|
|
| 7. |
- Bentley, Michael J., et al.
(författare)
-
A community-based geological reconstruction of Antarctic Ice Sheet deglaciation since the Last Glacial Maximum
- 2014
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 1-9
-
Tidskriftsartikel (refereegranskat)abstract
- A robust understanding of Antarctic Ice Sheet deglacial history since the Last Glacial Maximum is important in order to constrain ice sheet and glacial-isostatic adjustment models, and to explore the forcing mechanisms responsible for ice sheet retreat. Such understanding can be derived from a broad range of geological and glaciological datasets and recent decades have seen an upsurge in such data gathering around the continent and Sub-Antarctic islands. Here, we report a new synthesis of those datasets, based on an accompanying series of reviews of the geological data, organised by sector. We present a series of timeslice maps for 20 ka, 15 ka, 10 ka and 5 ka, including grounding line position and ice sheet thickness changes, along with a clear assessment of levels of confidence. The reconstruction shows that the Antarctic Ice sheet did not everywhere reach the continental shelf edge at its maximum, that initial retreat was asynchronous, and that the spatial pattern of deglaciation was highly variable, particularly on the inner shelf. The deglacial reconstruction is consistent with a moderate overall excess ice volume and with a relatively small Antarctic contribution to meltwater pulse la. We discuss key areas of uncertainty both around the continent and by time interval, and we highlight potential priorities for future work. The synthesis is intended to be a resource for the modelling and glacial geological community.
|
|
| 8. |
- Graham, Alastair G.C., et al.
(författare)
-
Rapid retreat of Thwaites Glacier in the pre-satellite era
- 2022
-
Ingår i: Nature Geoscience. - : Springer Science and Business Media LLC. - 1752-0894 .- 1752-0908. ; 15, s. 706-713
-
Tidskriftsartikel (refereegranskat)abstract
- Understanding the recent history of Thwaites Glacier, and the processes controlling its ongoing retreat, is key to projecting Antarctic contributions to future sea-level rise. Of particular concern is how the glacier grounding zone might evolve over coming decades where it is stabilized by sea-floor bathymetric highs. Here we use geophysical data from an autonomous underwater vehicle deployed at the Thwaites Glacier ice front, to document the ocean-floor imprint of past retreat from a sea-bed promontory. We show patterns of back-stepping sedimentary ridges formed daily by a mechanism of tidal lifting and settling at the grounding line at a time when Thwaites Glacier was more advanced than it is today. Over a duration of 5.5 months, Thwaites grounding zone retreated at a rate of >2.1 km per year—twice the rate observed by satellite at the fastest retreating part of the grounding zone between 2011 and 2019. Our results suggest that sustained pulses of rapid retreat have occurred at Thwaites Glacier in the past two centuries. Similar rapid retreat pulses are likely to occur in the near future when the grounding zone migrates back off stabilizing high points on the sea floor.
|
|
| 9. |
- Hodgson, Dominic A., et al.
(författare)
-
Terrestrial and submarine evidence for the extent and timing of the Last Glacial Maximum and the onset of deglaciation on the maritime-Antarctic and sub-Antarctic islands
- 2014
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791. ; 100, s. 137-158
-
Tidskriftsartikel (refereegranskat)abstract
- This paper is the maritime and sub Antarctic contribution to the Scientific Committee for Antarctic Research (SCAR) Past Antarctic Ice Sheet Dynamics (PAIS) community Antarctic Ice Sheet reconstruction. The overarching aim for all sectors of Antarctica was to reconstruct the Last Glacial Maximum (LGM) ice sheet extent and thickness, and map the subsequent deglaciation in a series of 5000 year time slices. However, our review of the literature found surprisingly few high quality chronological constraints on changing glacier extents on these timescales in the maritime and sub Antarctic sector. Therefore, in this paper we focus on an assessment of the terrestrial and offshore evidence for the LGM ice extent, establishing minimum ages for the onset of deglaciation, and separating evidence of deglaciation from LGM limits from those associated with later Holocene glacier fluctuations. Evidence included geomorphological descriptions of glacial landscapes, radiocarbon dated basal peat and lake sediment deposits, cosmogenic isotope ages of glacial features and molecular biological data. We propose a classification of the glacial history of the maritime and sub Antarctic islands based on this assembled evidence. These include: (Type I) islands which accumulated little or no LGM ice; (Type II) islands with a limited LGM ice extent but evidence of extensive earlier continental shelf glaciations; (Type III) seamounts and volcanoes unlikely to have accumulated significant LGM ice cover; (Type IV) islands on shallow shelves with both terrestrial and submarine evidence of LGM (and/or earlier) ice expansion; (Type V) Islands north of the Antarctic Polar Front with terrestrial evidence of LGM ice expansion; and (Type VI) islands with no data. Finally, we review the climatological and geomorphological settings that separate the glaciological history of the islands within this classification scheme. (C) 2014 The Authors. Published by Elsevier Ltd. All rights reserved.
|
|
| 10. |
- Larter, Robert D., et al.
(författare)
-
Reconstruction of changes in the Amundsen Sea and BellingshausenSea sector of the West Antarctic Ice Sheet since the Last GlacialMaximum
- 2013
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 56-86
-
Tidskriftsartikel (övrigt vetenskapligt/konstnärligt)abstract
- Marine and terrestrial geological and marine geophysical data that constrain deglaciation since the LastGlacial Maximum (LGM) of the sector of theWest Antarctic Ice Sheet (WAIS) draining into the AmundsenSea and Bellingshausen Sea have been collated and used as the basis for a set of time-slice reconstructions.The drainage basins in these sectors constitute a little more than one-quarter of the area ofthe WAIS, but account for about one-third of its surface accumulation. Their mass balance is becomingincreasingly negative, and therefore they account for an even larger fraction of currentWAIS discharge. Ifall of the ice in these sectors of the WAIS were discharged to the ocean, global sea level would rise byca 2 m.There is compelling evidence that grounding lines of palaeo-ice streams were at, or close to, thecontinental shelf edge along the Amundsen Sea and Bellingshausen Sea margins during the last glacialperiod. However, the few cosmogenic surface exposure ages and ice core data available from the interiorofWest Antarctica indicate that ice surface elevations there have changed little since the LGM. In the fewareas from which cosmogenic surface exposure ages have been determined near the margin of the icesheet, they generally suggest that there has been a gradual decrease in ice surface elevation since pre-Holocene times. Radiocarbon dates from glacimarine and the earliest seasonally open marine sedimentsin continental shelf cores that have been interpreted as providing approximate ages for post-LGMgrounding-line retreat indicate different trajectories of palaeo-ice stream recession in the Amundsen Seaand Bellingshausen Sea embayments. The areas were probably subject to similar oceanic, atmosphericand eustatic forcing, in which case the differences are probably largely a consequence of how topographicand geological factors have affected ice flow, and of topographic influences on snow accumulation andwarm water inflow across the continental shelf.Pauses in ice retreat are recorded where there are “bottle necks” in cross-shelf troughs in both embayments.The highest retreat rates presently constrained by radiocarbon dates from sediment cores arefound where the grounding line retreated across deep basins on the inner shelf in the Amundsen Sea,which is consistent with the marine ice sheet instability hypothesis. Deglacial ages from the Amundsen Sea Embayment (ASE) and Eltanin Bay (southern Bellingshausen Sea) indicate that the ice sheet hadalready retreated close to its modern limits by early Holocene time, which suggests that the rapid icethinning, flow acceleration, and grounding line retreat observed in this sector over recent decades areunusual in the context of the past 10,000 years.
|
|
