| 1. |
|
|
| 2. |
- Thompson, Paul M., et al.
(författare)
-
The ENIGMA Consortium : large-scale collaborative analyses of neuroimaging and genetic data
- 2014
-
Ingår i: BRAIN IMAGING BEHAV. - : Springer Science and Business Media LLC. - 1931-7557 .- 1931-7565. ; 8:2, s. 153-182
-
Tidskriftsartikel (refereegranskat)abstract
- The Enhancing NeuroImaging Genetics through Meta-Analysis (ENIGMA) Consortium is a collaborative network of researchers working together on a range of large-scale studies that integrate data from 70 institutions worldwide. Organized into Working Groups that tackle questions in neuroscience, genetics, and medicine, ENIGMA studies have analyzed neuroimaging data from over 12,826 subjects. In addition, data from 12,171 individuals were provided by the CHARGE consortium for replication of findings, in a total of 24,997 subjects. By meta-analyzing results from many sites, ENIGMA has detected factors that affect the brain that no individual site could detect on its own, and that require larger numbers of subjects than any individual neuroimaging study has currently collected. ENIGMA's first project was a genome-wide association study identifying common variants in the genome associated with hippocampal volume or intracranial volume. Continuing work is exploring genetic associations with subcortical volumes (ENIGMA2) and white matter microstructure (ENIGMA-DTI). Working groups also focus on understanding how schizophrenia, bipolar illness, major depression and attention deficit/hyperactivity disorder (ADHD) affect the brain. We review the current progress of the ENIGMA Consortium, along with challenges and unexpected discoveries made on the way.
|
|
| 3. |
- Schunkert, Heribert, et al.
(författare)
-
Large-scale association analysis identifies 13 new susceptibility loci for coronary artery disease
- 2011
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 43:4, s. 153-333
-
Tidskriftsartikel (refereegranskat)abstract
- We performed a meta-analysis of 14 genome-wide association studies of coronary artery disease (CAD) comprising 22,233 individuals with CAD (cases) and 64,762 controls of European descent followed by genotyping of top association signals in 56,682 additional individuals. This analysis identified 13 loci newly associated with CAD at P < 5 x 10(-8) and confirmed the association of 10 of 12 previously reported CAD loci. The 13 new loci showed risk allele frequencies ranging from 0.13 to 0.91 and were associated with a 6% to 17% increase in the risk of CAD per allele. Notably, only three of the new loci showed significant association with traditional CAD risk factors and the majority lie in gene regions not previously implicated in the pathogenesis of CAD. Finally, five of the new CAD risk loci appear to have pleiotropic effects, showing strong association with various other human diseases or traits.
|
|
| 4. |
- Anderson, Beverley H., et al.
(författare)
-
Mutations in CTC1, encoding conserved telomere maintenance component 1, cause Coats plus
- 2012
-
Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 44:3, s. 338-342
-
Tidskriftsartikel (refereegranskat)abstract
- Coats plus is a highly pleiotropic disorder particularly affecting the eye, brain, bone and gastrointestinal tract. Here, we show that Coats plus results from mutations in CTC1, encoding conserved telomere maintenance component 1, a member of the mammalian homolog of the yeast heterotrimeric CST telomeric capping complex. Consistent with the observation of shortened telomeres in an Arabidopsis CTC1 mutant and the phenotypic overlap of Coats plus with the telomeric maintenance disorders comprising dyskeratosis congenita, we observed shortened telomeres in three individuals with Coats plus and an increase in spontaneous gamma H2AX-positive cells in cell lines derived from two affected individuals. CTC1 is also a subunit of the alpha-accessory factor (AAF) complex, stimulating the activity of DNA polymerase-alpha primase, the only enzyme known to initiate DNA replication in eukaryotic cells. Thus, CTC1 may have a function in DNA metabolism that is necessary for but not specific to telomeric integrity.
|
|
| 5. |
- Hudson, Thomas J., et al.
(författare)
-
International network of cancer genome projects
- 2010
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 464:7291, s. 993-998
-
Tidskriftsartikel (refereegranskat)abstract
- The International Cancer Genome Consortium (ICGC) was launched to coordinate large-scale cancer genome studies in tumours from 50 different cancer types and/or subtypes that are of clinical and societal importance across the globe. Systematic studies of more than 25,000 cancer genomes at the genomic, epigenomic and transcriptomic levels will reveal the repertoire of oncogenic mutations, uncover traces of the mutagenic influences, define clinically relevant subtypes for prognosis and therapeutic management, and enable the development of new cancer therapies.
|
|
| 6. |
- Anderson, John B., et al.
(författare)
-
Ross Sea paleo-ice sheet drainage and deglacial history during and since the LGM
- 2014
-
Ingår i: Quaternary Science Reviews. - : Elsevier BV. - 0277-3791 .- 1873-457X. ; 100, s. 31-54
-
Tidskriftsartikel (refereegranskat)abstract
- Onshore and offshore studies show that an expanded, grounded ice sheet occupied the Ross Sea Embayment during the Last Glacial Maximum (LGM). Results from studies of till provenance and the orientation of geomorphic features on the continental shelf show that more than half of the grounded ice sheet consisted of East Antarctic ice flowing through Transantarctic Mountain (TAM) outlet glaciers; the remainder came from West Antarctica. Terrestrial data indicate little or no thickening in the upper catchment regions in both West and East Antarctica during the LGM. In contrast, evidence from the mouths of the southern and central TAM outlet glaciers indicate surface elevations between 1000 m and 1100 m (above present-day sea level). Farther north along the western margin of the Ross Ice Sheet, surface elevations reached 720 m on Ross Island, and 400 m at Terra Nova Bay. Evidence from Marie Byrd Land at the eastern margin of the ice sheet indicates that the elevation near the present-day grounding line was more than 800 m asl, while at Siple Dome in the central Ross Embayment, the surface elevation was about 950 m asl. Farther north, evidence that the ice sheet was grounded on the middle and the outer continental shelf during the LGM implies that surface elevations had to be at least 100 m above the LGM sea level. The apparent low surface profile and implied low basal shear stress in the central and eastern embayment suggests that although the ice streams may have slowed during the LGM, they remained active. Ice-sheet retreat from the western Ross Embayment during the Holocene is constrained by marine and terrestrial data. Ages from marine sediments suggest that the grounding line had retreated from its LGM outer shelf location only a few tens of kilometer to a location south of Coulman Island by similar to 13 ka BP. The ice sheet margin was located in the vicinity of the Drygalski Ice Tongue by similar to 11 ka BP, just north of Ross Island by similar to 7.8 ka BP, and near Hatherton Glacier by similar to 6.8 ka BP. Farther south, Be-10 exposure ages from glacial erratics on nunataks near the mouths of Reedy, Scott and Beardmore Glaciers indicate thinning during the mid to late Holocene, but the grounding line did not reach its present position until 2 to 3 ka BP. Marine dates, which are almost exclusively Acid Insoluble Organic (AIO) dates, are consistently older than those derived from terrestrial data. However, even these ages indicate that the ice sheet experienced significant retreat after similar to 13 ka BP. Geomorphic features indicate that during the final stages of ice sheet retreat ice flowing through the TAM remained grounded on the shallow western margin of Ross Sea. The timing of retreat from the central Ross Sea remains unresolved; the simplest reconstruction is to assume that the grounding line here started to retreat from the continental shelf more or less in step with the retreat from the western and eastern sectors. An alternative hypothesis, which relies on the validity of radiocarbon ages from marine sediments, is that grounded ice had retreated from the outer continental shelf prior to the LGM. More reliable ages from marine sediments in the central Ross Embayment are needed to test and validate this hypothesis.
|
|
| 7. |
- 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.
|
|
| 8. |
|
|
| 9. |
- Catalan, Jordi, et al.
(författare)
-
Global change revealed by palaeolimnological records from remote lakes : a review
- 2013
-
Ingår i: Journal of Paleolimnology. - : Springer Netherlands. - 0921-2728 .- 1573-0417. ; 49:3, s. 513-535
-
Tidskriftsartikel (refereegranskat)abstract
- Over recent decades, palaeolimnological records from remote sites have provided convincing evidence for the onset and development of several facets of global environmental change. Remote lakes, defined here as those occurring in high latitude or high altitude regions, have the advantage of not being overprinted by local anthropogenic processes. As such, many of these sites record broad-scale environmental changes, frequently driven by regime shifts in the Earth system. Here, we review a selection of studies from North America and Europe and discuss their broader implications. The history of investigation has evolved synchronously with the scope and awareness of environmental problems. An initial focus on acid deposition switched to metal and other types of pollutants, then climate change and eventually to atmospheric deposition-fertilising effects. However, none of these topics is independent of the other, and all of them affect ecosystem function and biodiversity in profound ways. Currently, remote lake palaeolimnology is developing unique datasets for each region investigated that benchmark current trends with respect to past, purely natural variability in lake systems. Fostering conceptual and methodological bridges with other environmental disciplines will upturn contribution of remote lake palaeolimnology in solving existing and emerging questions in global change science and planetary stewardship.
|
|
| 10. |
- Drezner, Jonathan A, et al.
(författare)
-
Electrocardiographic interpretation in athletes : the 'Seattle criteria'.
- 2013
-
Ingår i: British Journal of Sports Medicine. - : BMJ. - 0306-3674 .- 1473-0480. ; 47:3, s. 122-4
-
Tidskriftsartikel (refereegranskat)abstract
- Sudden cardiac death (SCD) is the leading cause of death in athletes during sport. Whether obtained for screening or diagnostic purposes, an ECG increases the ability to detect underlying cardiovascular conditions that may increase the risk for SCD. In most countries, there is a shortage of physician expertise in the interpretation of an athlete's ECG. A critical need exists for physician education in modern ECG interpretation that distinguishes normal physiological adaptations in athletes from abnormal findings suggestive of pathology. On 13-14 February 2012, an international group of experts in sports cardiology and sports medicine convened in Seattle, Washington, to define contemporary standards for ECG interpretation in athletes. The objective of the meeting was to develop a comprehensive training resource to help physicians distinguish normal ECG alterations in athletes from abnormal ECG findings that require additional evaluation for conditions associated with SCD.
|
|
