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- 2019
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Tidskriftsartikel (refereegranskat)
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- Feitosa, Mary F., et al.
(författare)
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Novel genetic associations for blood pressure identified via gene-alcohol interaction in up to 570K individuals across multiple ancestries
- 2018
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Ingår i: PLOS ONE. - : Public library science. - 1932-6203. ; 13:6
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Tidskriftsartikel (refereegranskat)abstract
- Heavy alcohol consumption is an established risk factor for hypertension; the mechanism by which alcohol consumption impact blood pressure (BP) regulation remains unknown. We hypothesized that a genome-wide association study accounting for gene-alcohol consumption interaction for BP might identify additional BP loci and contribute to the understanding of alcohol-related BP regulation. We conducted a large two-stage investigation incorporating joint testing of main genetic effects and single nucleotide variant (SNV)-alcohol consumption interactions. In Stage 1, genome-wide discovery meta-analyses in approximate to 131 K individuals across several ancestry groups yielded 3,514 SNVs (245 loci) with suggestive evidence of association (P <1.0 x 10(-5)). In Stage 2, these SNVs were tested for independent external replication in individuals across multiple ancestries. We identified and replicated (at Bonferroni correction threshold) five novel BP loci (380 SNVs in 21 genes) and 49 previously reported BP loci (2,159 SNVs in 109 genes) in European ancestry, and in multi-ancestry meta-analyses (P < 5.0 x 10(-8)). For African ancestry samples, we detected 18 potentially novel BP loci (P< 5.0 x 10(-8)) in Stage 1 that warrant further replication. Additionally, correlated meta-analysis identified eight novel BP loci (11 genes). Several genes in these loci (e.g., PINX1, GATA4, BLK, FTO and GABBR2 have been previously reported to be associated with alcohol consumption. These findings provide insights into the role of alcohol consumption in the genetic architecture of hypertension.
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- Klionsky, Daniel J., et al.
(författare)
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Guidelines for the use and interpretation of assays for monitoring autophagy
- 2012
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Ingår i: Autophagy. - : Informa UK Limited. - 1554-8635 .- 1554-8627. ; 8:4, s. 445-544
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Forskningsöversikt (refereegranskat)abstract
- In 2008 we published the first set of guidelines for standardizing research in autophagy. Since then, research on this topic has continued to accelerate, and many new scientists have entered the field. Our knowledge base and relevant new technologies have also been expanding. Accordingly, it is important to update these guidelines for monitoring autophagy in different organisms. Various reviews have described the range of assays that have been used for this purpose. Nevertheless, there continues to be confusion regarding acceptable methods to measure autophagy, especially in multicellular eukaryotes. A key point that needs to be emphasized is that there is a difference between measurements that monitor the numbers or volume of autophagic elements (e.g., autophagosomes or autolysosomes) at any stage of the autophagic process vs. those that measure flux through the autophagy pathway (i.e., the complete process); thus, a block in macroautophagy that results in autophagosome accumulation needs to be differentiated from stimuli that result in increased autophagic activity, defined as increased autophagy induction coupled with increased delivery to, and degradation within, lysosomes (in most higher eukaryotes and some protists such as Dictyostelium) or the vacuole (in plants and fungi). In other words, it is especially important that investigators new to the field understand that the appearance of more autophagosomes does not necessarily equate with more autophagy. In fact, in many cases, autophagosomes accumulate because of a block in trafficking to lysosomes without a concomitant change in autophagosome biogenesis, whereas an increase in autolysosomes may reflect a reduction in degradative activity. Here, we present a set of guidelines for the selection and interpretation of methods for use by investigators who aim to examine macroautophagy and related processes, as well as for reviewers who need to provide realistic and reasonable critiques of papers that are focused on these processes. These guidelines are not meant to be a formulaic set of rules, because the appropriate assays depend in part on the question being asked and the system being used. In addition, we emphasize that no individual assay is guaranteed to be the most appropriate one in every situation, and we strongly recommend the use of multiple assays to monitor autophagy. In these guidelines, we consider these various methods of assessing autophagy and what information can, or cannot, be obtained from them. Finally, by discussing the merits and limits of particular autophagy assays, we hope to encourage technical innovation in the field.
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- de Vries, Paul S., et al.
(författare)
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Multiancestry Genome-Wide Association Study of Lipid Levels Incorporating Gene-Alcohol Interactions
- 2019
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Ingår i: American Journal of Epidemiology. - : Oxford University Press. - 0002-9262 .- 1476-6256. ; 188:6, s. 1033-1054
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Tidskriftsartikel (refereegranskat)abstract
- A person's lipid profile is influenced by genetic variants and alcohol consumption, but the contribution of interactions between these exposures has not been studied. We therefore incorporated gene-alcohol interactions into a multiancestry genome-wide association study of levels of high-density lipoprotein cholesterol, low-density lipoprotein cholesterol, and triglycerides. We included 45 studies in stage 1 (genome-wide discovery) and 66 studies in stage 2 (focused follow-up), for a total of 394,584 individuals from 5 ancestry groups. Analyses covered the period July 2014-November 2017. Genetic main effects and interaction effects were jointly assessed by means of a 2-degrees-of-freedom (df) test, and a 1-df test was used to assess the interaction effects alone. Variants at 495 loci were at least suggestively associated (P < 1 x 10(-6)) with lipid levels in stage 1 and were evaluated in stage 2, followed by combined analyses of stage 1 and stage 2. In the combined analysis of stages 1 and 2, a total of 147 independent loci were associated with lipid levels at P < 5 x 10(-8) using 2-df tests, of which 18 were novel. No genome-wide-significant associations were found testing the interaction effect alone. The novel loci included several genes (proprotein convertase subtilisin/kexin type 5 (PCSK5), vascular endothelial growth factor B (VEGFB), and apolipoprotein B mRNA editing enzyme, catalytic polypeptide 1 (APOBEC1) complementation factor (A1CF)) that have a putative role in lipid metabolism on the basis of existing evidence from cellular and experimental models.
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| 6. |
- Fan, Lulu, et al.
(författare)
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ALMA Reveals a Gas-rich, Maximum Starburst in the Hyperluminous, Dust-obscured Quasar W0533-3401 at z similar to 2.9
- 2019
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 887:1
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Tidskriftsartikel (refereegranskat)abstract
- We present ALMA observations and multiwavelength spectral energy distribution analysis in a Wide-field Infrared Survey Explorer-selected, hyperluminous dust-obscured quasar W0533-3401 at z = 2.9. We derive the physical properties of each of its components, such as molecular gas, stars, dust, and the central supermassive black hole (SMBH). Both the dust continuum at 3 mm and the CO (3-2) line are detected. The derived molecular gas mass M-gas = 8.4 x 10(10) M-circle dot and its fraction f(gas) = 0.7 suggest that W0533-3401 is gas-rich. The star formation rate (SFR) has been estimated to be similar to 3000-7000M(circle dot) yr(-1) by using different methods. The high values of SFR and specific SFR suggest that W0533-3401 is a maximum starburst. The corresponding gas depletion timescales are very short (t(depl) similar to 12-28 Myr). The CO (3-2) emission line is marginally resolved and has a velocity gradient, which is possibly due to a rotating gas disk, gas outflow, or merger. Finally, we infer the black hole mass growth rate of W0533-3401 ((M)over dot(BH) = 49 M-circle dot yr(-1)), which suggests a rapid growth of the central SMBH. The observed black hole to stellar mass ratio M-BH/M-* of W0533-3401, which is dependent on the adopted Eddington ratio, is over one order of magnitude higher than the local value, and is evolving toward the evolutionary trend of unobscured quasars. Our results are consistent with the scenario that W0533-3401, with both a gas-rich maximum starburst and a rapid black hole growth, is experiencing a short transition phase toward an unobscured quasar.
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- Zhang, Huai, et al.
(författare)
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A global survey on the use of the international classification of diseases codes for metabolic dysfunction-associated fatty liver disease.
- 2024
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Ingår i: Hepatology international. - 1936-0541.
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Tidskriftsartikel (refereegranskat)abstract
- With the implementation of the 11th edition of the International Classification of Diseases (ICD-11) and the publication of the metabolic dysfunction-associated fatty liver disease (MAFLD) nomenclature in 2020, it is important to establish consensus for the coding of MAFLD in ICD-11. This will inform subsequent revisions of ICD-11.Using the Qualtrics XM and WJX platforms, questionnaires were sent online to MAFLD-ICD-11 coding collaborators, authors of papers, and relevant association members.A total of 890 international experts in various fields from 61 countries responded to the survey. We also achieved full coverage of provincial-level administrative regions in China. 77.1% of respondents agreed that MAFLD should be represented in ICD-11 by updating NAFLD, with no significant regional differences (77.3% in Asia and 76.6% in non-Asia, p=0.819). Over 80% of respondents agreed or somewhat agreed with the need to assign specific codes for progressive stages of MAFLD (i.e. steatohepatitis) (92.2%), MAFLD combined with comorbidities (84.1%), or MAFLD subtypes (i.e., lean, overweight/obese, and diabetic) (86.1%).This global survey by a collaborative panel of clinical, coding, health management and policy experts, indicates agreement that MAFLD should be coded in ICD-11. The data serves as a foundation for corresponding adjustments in the ICD-11 revision.
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| 8. |
- Zhou, Jing, et al.
(författare)
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Dense Gas and Star Formation in Nearby Infrared-bright Galaxies: APEX Survey of HCN and HCO+ J=2 -> 1
- 2022
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Ingår i: Astrophysical Journal. - : American Astronomical Society. - 1538-4357 .- 0004-637X. ; 936:1
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Tidskriftsartikel (refereegranskat)abstract
- Both Galactic and extragalactic studies of star formation suggest that stars form directly from dense molecular gas. To trace such high volume density gas, HCN and HCO+ J = 1 -> 0 have been widely used for their high dipole moments, relatively high abundances, and often being the strongest lines after CO. However, HCN and HCO+ J = 1 -> 0 emission could arguably be dominated by the gas components at low volume densities. The HCN J = 2 -> 1 and HCO+ J = 2 -> 1 transitions, with more suitable critical densities (1.6 x 10(6) and 2.8 x 10(5) cm(-3)) and excitation requirements, would trace typical dense gas closely related to star formation. Here we report new observations of HCN J = 2 -> 1 and HCO+ J = 2 -> 1 toward 17 nearby infrared-bright galaxies with the APEX 12 m telescope. The correlation slopes between the luminosities of HCN J = 2 -> 1 and HCO+ J = 2 -> 1 and total infrared emission are 1.03 +/- 0.05 and 1.00 +/- 0.05, respectively. The correlations of their surface densities, normalized with the area of radio/submillimeter continuum, show even tighter relations (slopes: 0.99 +/- 0.03 and 1.02 +/- 0.03). The eight active galactic nucleus (AGN)-dominated galaxies show no significant difference from the 11 star-formation-dominated galaxies in the above relations. The average HCN/HCO+ ratios are 1.15 +/- 0.26 and 0.98 +/- 0.42 for AGN- and star-formation-dominated galaxies, respectively, without obvious dependencies on infrared luminosity, dust temperature, or infrared pumping. The Magellanic Clouds roughly follow the same correlations, expanding to 8 orders of magnitude. On the other hand, ultraluminous infrared galaxies with AGNs systematically lie above the correlations, indicating potential biases introduced by AGNs.
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