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- Kanoni, Stavroula, et al.
(författare)
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Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
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Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
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Tidskriftsartikel (refereegranskat)abstract
- Genetic variants within nearly 1000 loci are known to contribute to modulation of blood lipid levels. However, the biological pathways underlying these associations are frequently unknown, limiting understanding of these findings and hindering downstream translational efforts such as drug target discovery.To expand our understanding of the underlying biological pathways and mechanisms controlling blood lipid levels, we leverage a large multi-ancestry meta-analysis (N=1,654,960) of blood lipids to prioritize putative causal genes for 2286 lipid associations using six gene prediction approaches. Using phenome-wide association (PheWAS) scans, we identify relationships of genetically predicted lipid levels to other diseases and conditions. We confirm known pleiotropic associations with cardiovascular phenotypes and determine novel associations, notably with cholelithiasis risk. We perform sex-stratified GWAS meta-analysis of lipid levels and show that 3-5% of autosomal lipid-associated loci demonstrate sex-biased effects. Finally, we report 21 novel lipid loci identified on the X chromosome. Many of the sex-biased autosomal and X chromosome lipid loci show pleiotropic associations with sex hormones, emphasizing the role of hormone regulation in lipid metabolism.Taken together, our findings provide insights into the biological mechanisms through which associated variants lead to altered lipid levels and potentially cardiovascular disease risk.
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| 2. |
- Lo Mauro, Antonella, et al.
(författare)
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Adaptation of lung, chest wall, and respiratory muscles during pregnancy : preparing for birth
- 2019
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Ingår i: Journal of applied physiology. - : AMER PHYSIOLOGICAL SOC. - 8750-7587 .- 1522-1601. ; 127:6, s. 1640-1650
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Tidskriftsartikel (refereegranskat)abstract
- A plethora of physiological and biochemical changes occur during normal pregnancy. The changes in the respiratory system have not been as well elucidated, in part because radioimaging is usually avoided during pregnancy. We aimed to use several noninvasive methods to characterize the adaptation of the respiratory system during the full course of pregnancy in preparation for childbirth. Eighteen otherwise healthy women (32.3 +/- 2.8 yr) were recruited during early pregnancy. Spirometry, optoelectronic plethysmography, and ultrasonography were used to study changes in chest wall geometry, breathing pattern, lung and thoraco-abdominal volume variations, and diaphragmatic thickness in the first, second, and third trimesters. A group of nonpregnant women were used as control subjects. During the course of pregnancy, we observed a reorganization of rib cage geometry, in shape but not in volume. Despite the growing uterus, there was no lung restriction (forced vital capacity: 101 +/- 15% predicted), but we did observe reduced rib cage expansion. Breathing frequency and diaphragmatic contribution to tidal volume and inspiratory capacity increased. Diaphragm thickness was maintained (1st trimester: 2.7 +/- 0.8 mm, 3rd trimester: 2.5 +/- 0.9 mm; P = 0.187), possibly indicating a conditioning effect to compensate for the effects of the growing uterus. We conclude that pregnancy preserved lung volumes, abdominal muscles, and the diaphragm at the expense of rib cage muscles. NEW & NOTEWORTHY Noninvasive analysis of the kinematics of the chest wall and the diaphragm during resting conditions in pregnant women revealed significant changes in the pattern of thoracoabdominal breathing across the trimesters. That is, concomitant with the progressive changes of chest wall shape, the diaphragm increased its contribution to both spontaneous and maximal breathing, maintaining its thickness despite its lengthening due to the growing uterus. These results suggest that during pregnancy the diaphragm is conditioned to optimize its active role provided during parturition.
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