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- Sawcer, Stephen, et al.
(författare)
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Genetic risk and a primary role for cell-mediated immune mechanisms in multiple sclerosis
- 2011
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 476:7359, s. 214-219
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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.
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- Beecham, Ashley H, et al.
(författare)
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Analysis of immune-related loci identifies 48 new susceptibility variants for multiple sclerosis.
- 2013
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Ingår i: Nature genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 45:11, s. 1353-60
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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.
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- Harri, A.-M., et al.
(författare)
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Mars Science Laboratory relative humidity observations: Initial results
- 2014
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Ingår i: Journal of Geophysical Research - Planets. - 2169-9097 .- 2169-9100. ; 119:9, s. 2132-2147
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Tidskriftsartikel (refereegranskat)abstract
- The Mars Science Laboratory (MSL) made a successful landing at Gale crater early August 2012. MSL has an environmental instrument package called the Rover Environmental Monitoring Station (REMS) as a part of its scientific payload. REMS comprises instrumentation for the observation of atmospheric pressure, temperature of the air, ground temperature, wind speed and direction, relative humidity (REMS-H), and UV measurements. We concentrate on describing the REMS-H measurement performance and initial observations during the first 100 MSL sols as well as constraining the REMS-H results by comparing them with earlier observations and modeling results. The REMS-H device is based on polymeric capacitive humidity sensors developed by Vaisala Inc., and it makes use of transducer electronics section placed in the vicinity of the three humidity sensor heads. The humidity device is mounted on the REMS boom providing ventilation with the ambient atmosphere through a filter protecting the device from airborne dust. The final relative humidity results appear to be convincing and are aligned with earlier indirect observations of the total atmospheric precipitable water content. The water mixing ratio in the atmospheric surface layer appears to vary between 30 and 75 ppm. When assuming uniform mixing, the precipitable water content of the atmosphere is ranging from a few to six precipitable micrometers.
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