| 161. |
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| 162. |
- Eicher, John D., et al.
(författare)
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Platelet-Related Variants Identified by Exomechip Meta-analysis in 157,293 Individuals
- 2016
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Ingår i: American Journal of Human Genetics. - : Elsevier BV. - 0002-9297 .- 1537-6605. ; 99:1, s. 40-55
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Tidskriftsartikel (refereegranskat)abstract
- Platelet production, maintenance, and clearance are tightly controlled processes indicative of platelets' important roles in hemostasis and thrombosis. Platelets are common targets for primary and secondary prevention of several conditions. They are monitored clinically by complete blood counts, specifically with measurements of platelet count (PLT) and mean platelet volume (MPV). Identifying genetic effects on PLT and MPV can provide mechanistic insights into platelet biology and their role in disease. Therefore, we formed the Blood Cell Consortium (BCX) to perform a large-scale meta-analysis of Exomechip association results for PLT and MPV in 157,293 and 57,617 individuals, respectively. Using the low-frequency/rare coding variant-enriched Exomechip genotyping array, we sought to identify genetic variants associated with PLT and MPV. In addition to confirming 47 known PLT and 20 known MPV associations, we identified 32 PLT and 18 MPV associations not previously observed in the literature across the allele frequency spectrum, including rare large effect (FCER1A), low-frequency (IQGAP2, MAP1A, LY75), and common(ZMIZ2, SMG6, PEAR1, ARFGAP3/PACSIN2) variants. Several variants associated with PLT/MPV(PEAR1, MRVI1, PTGES3) were also associated with platelet reactivity. In concurrent BCX analyses, there was overlap of platelet-associated variants with red (MAP1A, TMPRSS6, ZMIZ2) and white (PEAR1, ZMIZ2, LY75) blood cell traits, suggesting common regulatory pathways with shared genetic architecture among these hematopoietic lineages. Our large-scale Exomechip analyses identified previously undocumented associations with platelet traits and further indicate that several complex quantitative hematological, lipid, and cardiovascular traits share genetic factors.
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| 163. |
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| 164. |
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| 165. |
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| 166. |
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| 167. |
- Zheng, Hou-Feng, et al.
(författare)
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Whole-genome sequencing identifies EN1 as a determinant of bone density and fracture
- 2015
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 526:7571, s. 112-
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Tidskriftsartikel (refereegranskat)abstract
- The extent to which low-frequency (minor allele frequency (MAF) between 1-5%) and rare (MAF <= 1%) variants contribute to complex traits and disease in the general population is mainly unknown. Bone mineral density (BMD) is highly heritable, a major predictor of osteoporotic fractures, and has been previously associated with common genetic variants(1-8), as well as rare, population specific, coding variants(9). Here we identify novel non-coding genetic variants with large effects on BMD (n(total) = 53,236) and fracture (n(total) = 508,253) in individuals of European ancestry from the general population. Associations for BMD were derived from whole-genome sequencing (n = 2,882 from UK10K (ref. 10); a population-based genome sequencing consortium), whole-exome sequencing (n = 3,549), deep imputation of genotyped samples using a combined UK10K/1000 Genomes reference panel (n = 26,534), and de novo replication genotyping (n = 20,271). We identified a low-frequency non-coding variant near a novel locus, EN1, with an effect size fourfold larger than the mean of previously reported common variants for lumbar spine BMD8 (rs11692564(T), MAF51.6%, replication effect size510.20 s.d., P-meta = 2 x 10(-14)), which was also associated with a decreased risk of fracture (odds ratio = 0.85; P = 2 x 10(-11); ncases = 98,742 and ncontrols = 409,511). Using an En1cre/flox mouse model, we observed that conditional loss of En1 results in low bone mass, probably as a consequence of high bone turnover. We also identified a novel low frequency non-coding variant with large effects on BMD near WNT16 (rs148771817(T), MAF = 1.2%, replication effect size +10.41 s.d., P-meta = 1 x 10(-11)). In general, there was an excess of association signals arising from deleterious coding and conserved non-coding variants. These findings provide evidence that low-frequency non-coding variants have large effects on BMD and fracture, thereby providing rationale for whole-genome sequencing and improved imputation reference panels to study the genetic architecture of complex traits and disease in the general population.
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| 168. |
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| 169. |
- Hernandez-Molina, F. J., et al.
(författare)
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Oceanographic processes and morphosedimentary products along the Iberian margins: A new multidisciplinary approach
- 2016
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Ingår i: Marine Geology. - : Elsevier BV. - 0025-3227. ; 378, s. 127-156
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of bottom-currents and associated oceanographic processes (e.g., overflows, barotropic tidal currents) including intermittent processes (e.g., vertical eddies, deep sea storms, horizontal vortices, internal waves and tsunamis) is rapidly evolving. Many deep-water processes remain poorly understood due to limited direct observations, but can generate significant depositional and erosional features on both short and long term time scales. This paper represents a review work, which describes for the first time these oceanographic processes and examines their potential role in the sedimentary features along the Iberian continental margins. This review explores the implications of the studied processes, given their secondary role relative to other factors such as mass-transport and turbiditic processes, and highlights three major results: a) contourite depositional and erosional features are ubiquitous along the margins, indicating that bottom currents and associated oceanographic processes control the physiography and sedimentation; b) the position of interfaces between major water masses and their vertical and spatial variation in time specifically appears to exert primary control in determining major morphologic changes along the slope gradient, including the contourite terraces development; and c) contourites deposits exhibit greater variation than the established fades model suggests. Therefore, a consistent facies model however faces substantial challenges in terms of the wide range of oceanographic processes that can influence in their development. An integrated interpretation of these oceanographic processes requires an understanding of contourites, seafloor features, their spatial and temporal evolution, and the near-bottom flows that form them. This approach will synthesize oceanographic data, seafloor morphology, sediments and seismic images to improve our knowledge of permanent and intermittent processes around Iberia, and evaluate their conceptual and regional role in the margin's sedimentary evolution. Given their complexes, three-dimensional and temporally-variable nature, integration of these processes into sedimentary, oceanographic and climatological frameworks will require a multidisciplinary approach that includes Geology, Physical oceanography, Paleoceanography and Benthic Biology.
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| 170. |
- Hernandez Molina, Javier, et al.
(författare)
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Oceanographic processes and products around the Iberian margin: a new multidisciplinary approach : Procesos oceanográficos y sus productos alrededor del margen de Iberia: una nueva aproximación multidisciplinar
- 2015
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Ingår i: Boletín Geológico y Minero. - 0366-0176 .- 0366-0176. ; 126:2-3, s. 279-326
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Tidskriftsartikel (refereegranskat)abstract
- Our understanding of the role of bottom-current and associated oceanographic processes (as overflows, barotropic currents, tides or intermittent processes like giant vertical eddies, deep sea storms, horizontal vortices, internal waves and tsunamis) is rapidly improving. But, most of these oceanographic deep-water processes remains poorly understood and have been rarely observed but believed to be capable of generating depositional and erosional features in many contexts at both short and long term. In present compilation we described these oceanographic processes including examples or their potential role in the sedimentation processes around the Iberia margin. Importance of these processes is highlighted and its implication discussed to demonstrate that these oceanographic processes are very important is affecting the shape and evolution of the Iberian continental margin and adjacent oceanic basins although is not still considered as important as other factors as mass-transport deposits and turbiditic processes. To have a better understanding on the implication of all these oceanographic processes connections have to be made between (contourite) sea-floor features, their spatial and temporal evolution, and the near-bottom flows that form them. The only way to achieve that in next decades is by a more intensive collaboration between specialist from Geology, Oceanography and Benthic Biology in new multi-disciplinary studies. Consequently, further multi-disciplinary approach uses oceanographic data, sea-floor morphology, sediments and seismic characterization will be essential for improve our knowledge of these permanent and intermittent processes around Iberia and evaluate their conceptual and regional role in the margins evolution over time and space.
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