| 1. |
- Kupers, LK, et al.
(författare)
-
Meta-analysis of epigenome-wide association studies in neonates reveals widespread differential DNA methylation associated with birthweight
- 2019
-
Ingår i: Nature communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 10:1, s. 1893-
-
Tidskriftsartikel (refereegranskat)abstract
- Birthweight is associated with health outcomes across the life course, DNA methylation may be an underlying mechanism. In this meta-analysis of epigenome-wide association studies of 8,825 neonates from 24 birth cohorts in the Pregnancy And Childhood Epigenetics Consortium, we find that DNA methylation in neonatal blood is associated with birthweight at 914 sites, with a difference in birthweight ranging from −183 to 178 grams per 10% increase in methylation (PBonferroni < 1.06 x 10−7). In additional analyses in 7,278 participants, <1.3% of birthweight-associated differential methylation is also observed in childhood and adolescence, but not adulthood. Birthweight-related CpGs overlap with some Bonferroni-significant CpGs that were previously reported to be related to maternal smoking (55/914, p = 6.12 x 10−74) and BMI in pregnancy (3/914, p = 1.13x10−3), but not with those related to folate levels in pregnancy. Whether the associations that we observe are causal or explained by confounding or fetal growth influencing DNA methylation (i.e. reverse causality) requires further research.
|
|
| 2. |
- Campbell, PJ, et al.
(författare)
-
Pan-cancer analysis of whole genomes
- 2020
-
Ingår i: Nature. - : Springer Science and Business Media LLC. - 1476-4687 .- 0028-0836. ; 578:7793, s. 82-
-
Tidskriftsartikel (refereegranskat)abstract
- Cancer is driven by genetic change, and the advent of massively parallel sequencing has enabled systematic documentation of this variation at the whole-genome scale1–3. Here we report the integrative analysis of 2,658 whole-cancer genomes and their matching normal tissues across 38 tumour types from the Pan-Cancer Analysis of Whole Genomes (PCAWG) Consortium of the International Cancer Genome Consortium (ICGC) and The Cancer Genome Atlas (TCGA). We describe the generation of the PCAWG resource, facilitated by international data sharing using compute clouds. On average, cancer genomes contained 4–5 driver mutations when combining coding and non-coding genomic elements; however, in around 5% of cases no drivers were identified, suggesting that cancer driver discovery is not yet complete. Chromothripsis, in which many clustered structural variants arise in a single catastrophic event, is frequently an early event in tumour evolution; in acral melanoma, for example, these events precede most somatic point mutations and affect several cancer-associated genes simultaneously. Cancers with abnormal telomere maintenance often originate from tissues with low replicative activity and show several mechanisms of preventing telomere attrition to critical levels. Common and rare germline variants affect patterns of somatic mutation, including point mutations, structural variants and somatic retrotransposition. A collection of papers from the PCAWG Consortium describes non-coding mutations that drive cancer beyond those in the TERT promoter4; identifies new signatures of mutational processes that cause base substitutions, small insertions and deletions and structural variation5,6; analyses timings and patterns of tumour evolution7; describes the diverse transcriptional consequences of somatic mutation on splicing, expression levels, fusion genes and promoter activity8,9; and evaluates a range of more-specialized features of cancer genomes8,10–18.
|
|
| 3. |
|
|
| 4. |
|
|
| 5. |
|
|
| 6. |
|
|
| 7. |
|
|
| 8. |
|
|
| 9. |
|
|
| 10. |
|
|
| 11. |
|
|
| 12. |
|
|
| 13. |
|
|
| 14. |
|
|
| 15. |
|
|
| 16. |
|
|
| 17. |
|
|
| 18. |
|
|
| 19. |
- Lagerstrand, L, et al.
(författare)
-
Tidal volume forced expiration in asthmatic infants: reproducibility and reversibility tests
- 2002
-
Ingår i: Respiration. - : S. Karger AG. - 0025-7931 .- 1423-0356. ; 69:5, s. 389-396
-
Tidskriftsartikel (refereegranskat)abstract
- <i>Background:</i> The tidal volume forced expiration technique used in infants is considered as the first practical noninvasive method of assessing airway physiology in infants. However, its role has been discussed mainly due to the high variability of the derived parameters. <i>Objectives:</i> The aim of the study was to assess the reproducibility of a complete measurement with the tidal volume forced expiration technique in infants as measured by the maximal flow at FRC (v̇<sub>max</sub>FRC). A second aim was to evaluate the bronchial reversibility test in infant asthma. <i>Methods:</i> Thirty infants with asthma were investigated with the tidal volume forced expiration technique twice with 10 min in between and a third time 10 min after inhalation of terbutalin 0.5 mg. <i>Results:</i> The mean v̇<sub>max</sub>FRC in the first investigation was 285 ml·s<sup>–1</sup> (coefficient of variation 57%), unchanged in the second investigation and significantly lower than the mean predicted value of 404 ml·s<sup>–1</sup>. The relative difference between the 2 investigations of v̇<sub>max</sub>FRC was mean 10.5% (SD 8.4) of the absolute v̇<sub>max</sub>FRC value and independent of the size of this v̇<sub>max</sub>FRC value. The 95% confidence interval for individual changes would then be up to 27% (mean + 2 SD). The infants with the lowest v̇<sub>max</sub>FRC percent predicted decreased further in v̇<sub>max</sub>FRC after inhalation of the bronchodilator (p < 0.05). <i>Conclusions:</i> The tidal volume forced expiration technique was able to measure flow at late expiration with the same reproducibility as seen with spirometry in adults, even if the flow was low. We found the technique acceptable for clinical practice and research, but the results from reversibility tests are difficult to interpret. A significant change of v̇<sub>max</sub>FRC would, however, be 27% or more.
|
|
| 20. |
|
|
| 21. |
|
|
| 22. |
|
|
| 23. |
|
|
| 24. |
|
|
