| 1. |
- Teslovich, Tanya M., et al.
(författare)
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Biological, clinical and population relevance of 95 loci for blood lipids
- 2010
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 466:7307, s. 707-713
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Tidskriftsartikel (refereegranskat)abstract
- Plasma concentrations of total cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol and triglycerides are among the most important risk factors for coronary artery disease (CAD) and are targets for therapeutic intervention. We screened the genome for common variants associated with plasma lipids in >100,000 individuals of European ancestry. Here we report 95 significantly associated loci (P<5 x 10(-8)), with 59 showing genome-wide significant association with lipid traits for the first time. The newly reported associations include single nucleotide polymorphisms (SNPs) near known lipid regulators (for example, CYP7A1, NPC1L1 and SCARB1) as well as in scores of loci not previously implicated in lipoprotein metabolism. The 95 loci contribute not only to normal variation in lipid traits but also to extreme lipid phenotypes and have an impact on lipid traits in three non-European populations (East Asians, South Asians and African Americans). Our results identify several novel loci associated with plasma lipids that are also associated with CAD. Finally, we validated three of the novel genes-GALNT2, PPP1R3B and TTC39B-with experiments in mouse models. Taken together, our findings provide the foundation to develop a broader biological understanding of lipoprotein metabolism and to identify new therapeutic opportunities for the prevention of CAD.
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| 2. |
- Hubert, D., et al.
(författare)
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Ground-based assessment of the bias and long-term stability of 14 limb and occultation ozone profile data records
- 2016
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Ingår i: Atmospheric Measurement Techniques. - : Copernicus GmbH. - 1867-1381 .- 1867-8548. ; 9:6, s. 2497-2534
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Tidskriftsartikel (refereegranskat)abstract
- The ozone profile records of a large number of limb and occultation satellite instruments are widely used to address several key questions in ozone research. Further progress in some domains depends on a more detailed understanding of these data sets, especially of their long-term stability and their mutual consistency. To this end, we made a systematic assessment of 14 limb and occultation sounders that, together, provide more than three decades of global ozone profile measurements. In particular, we considered the latest operational Level-2 records by SAGE II, SAGE III, HALOE, UARS MLS, Aura MLS, POAM II, POAM III, OSIRIS, SMR, GOMOS, MIPAS, SCIAMACHY, ACE-FTS and MAESTRO. Central to our work is a consistent and robust analysis of the comparisons against the ground-based ozonesonde and stratospheric ozone lidar networks. It allowed us to investigate, from the troposphere up to the stratopause, the following main aspects of satellite data quality: long-term stability, overall bias and short-term variability, together with their dependence on geophysical parameters and profile representation. In addition, it permitted us to quantify the overall consistency between the ozone profilers. Generally, we found that between 20 and 40km the satellite ozone measurement biases are smaller than ±5%, the short-term variabilities are less than 5-12% and the drifts are at most ±5%decade-1 (or even ±3%decade-1 for a few records). The agreement with ground-based data degrades somewhat towards the stratopause and especially towards the tropopause where natural variability and low ozone abundances impede a more precise analysis. In part of the stratosphere a few records deviate from the preceding general conclusions; we identified biases of 10% and more (POAM II and SCIAMACHY), markedly higher single-profile variability (SMR and SCIAMACHY) and significant long-term drifts (SCIAMACHY, OSIRIS, HALOE and possibly GOMOS and SMR as well). Furthermore, we reflected on the repercussions of our findings for the construction, analysis and interpretation of merged data records. Most notably, the discrepancies between several recent ozone profile trend assessments can be mostly explained by instrumental drift. This clearly demonstrates the need for systematic comprehensive multi-instrument comparison analyses.
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| 3. |
- van der Harst, Pim, et al.
(författare)
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Seventy-five genetic loci influencing the human red blood cell
- 2012
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Ingår i: Nature. - : Springer Science and Business Media LLC. - 0028-0836 .- 1476-4687. ; 492:7429, s. 369-375
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Tidskriftsartikel (refereegranskat)abstract
- Anaemia is a chief determinant of global ill health, contributing to cognitive impairment, growth retardation and impaired physical capacity. To understand further the genetic factors influencing red blood cells, we carried out a genome-wide association study of haemoglobin concentration and related parameters in up to 135,367 individuals. Here we identify 75 independent genetic loci associated with one or more red blood cell phenotypes at P < 10(-8), which together explain 4-9% of the phenotypic variance per trait. Using expression quantitative trait loci and bioinformatic strategies, we identify 121 candidate genes enriched in functions relevant to red blood cell biology. The candidate genes are expressed preferentially in red blood cell precursors, and 43 have haematopoietic phenotypes in Mus musculus or Drosophila melanogaster. Through open-chromatin and coding-variant analyses we identify potential causal genetic variants at 41 loci. Our findings provide extensive new insights into genetic mechanisms and biological pathways controlling red blood cell formation and function.
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