| 1. |
- Heald, Adrian H., et al.
(författare)
-
Genetically defined favourable adiposity is not associated with a clinically meaningful difference in clinical course in people with type 2 diabetes but does associate with a favourable metabolic profile
- 2021
-
Ingår i: Diabetic Medicine. - : John Wiley & Sons. - 0742-3071 .- 1464-5491. ; 38:9
-
Tidskriftsartikel (refereegranskat)abstract
- AimsChange in weight, HbA1c, lipids, blood pressure and cardiometabolic events over time is variable in individuals with type 2 diabetes. We hypothesized that people with a genetic predisposition to a more favourable adiposity distribution could have a less severe clinical course/progression.MethodsWe involved people with type 2 diabetes from two UK‐based cohorts: 11,914 individuals with GP follow‐up data from the UK Biobank and 723 from Salford. We generated a ‘favourable adiposity’ genetic score and conducted cross‐sectional and longitudinal studies to test its association with weight, BMI, lipids, blood pressure, medication use and risk of myocardial infarction and stroke using 15 follow‐up time points with 1‐year intervals.ResultsThe ‘favourable adiposity’ genetic score was cross‐sectionally associated with higher weight (effect size per 1 standard deviation higher genetic score: 0.91kg [0.59,1.23]) and BMI (0.30kg/m2 [0.19,0.40]), but higher high‐density lipoprotein (0.02mmol/L [0.01,0.02]) and lower triglycerides (‐0.04mmol/L [‐0.07,‐0.02]) in the UK Biobank at baseline, and this pattern of association was consistent across follow‐up.There was a trend for participants with higher ‘favourable adiposity’ genetic score to have lower risk of myocardial infarction and/or stroke (odds ratio 0.79 [0.62,1.00]) compared to those with lower score. A one standard deviation higher score was associated with lower odds of using lipid‐lowering (0.91 [0.86,0.97]) and anti‐hypertensive medication (0.95 [0.91,0.99]).ConclusionsIn individuals with type 2 diabetes, having more ‘favourable adiposity’ alleles is associated with a marginally better lipid profile long‐term and having lower odds of requiring lipid‐lowering or anti‐hypertensive medication in spite of relatively higher adiposity.
|
|
| 2. |
- Kanoni, Stavroula, et al.
(författare)
-
Implicating genes, pleiotropy, and sexual dimorphism at blood lipid loci through multi-ancestry meta-analysis.
- 2022
-
Ingår i: Genome biology. - : Springer Science and Business Media LLC. - 1474-760X .- 1465-6906 .- 1474-7596. ; 23:1
-
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.
|
|
| 3. |
- Lundgren, Jens D, et al.
(författare)
-
Long-Term Benefits from Early Antiretroviral Therapy Initiation in HIV Infection.
- 2023
-
Ingår i: NEJM evidence. - : Massachusetts Medical Society. - 2766-5526. ; 2:3
-
Tidskriftsartikel (refereegranskat)abstract
- For people with HIV and CD4+ counts >500 cells/mm3, early initiation of antiretroviral therapy (ART) reduces serious AIDS and serious non-AIDS (SNA) risk compared with deferral of treatment until CD4+ counts are <350 cells/mm3. Whether excess risk of AIDS and SNA persists once ART is initiated for those who defer treatment is uncertain.The Strategic Timing of AntiRetroviral Treatment (START) trial, as previously reported, randomly assigned 4684 ART-naive HIV-positive adults with CD4+ counts .500 cells/mm3 to immediate treatment initiation after random assignment (n = 2325) or deferred treatment (n= 2359). In 2015, a 57% lower risk of the primary end point (AIDS, SNA, or death) for the immediate group was reported, and the deferred group was offered ART. This article reports the follow-up that continued to December 31, 2021. Cox proportional-hazards models were used to compare hazard ratios for the primary end point from randomization through December 31, 2015, versus January 1, 2016, through December 31, 2021.Through December 31, 2015, approximately 7 months after the cutoff date from the previous report, the median CD4+ count was 648 and 460 cells/mm3 in the immediate and deferred groups, respectively, at treatment initiation. The percentage of follow-up time spent taking ART was 95% and 36% for the immediate and deferred groups, respectively, and the time-averaged CD4+ difference was 199 cells/mm3. After January 1, 2016, the percentage of follow-up time on treatment was 97.2% and 94.1% for the immediate and deferred groups, respectively, and the CD4+ count difference was 155 cells/mm3. After January 1, 2016, a total of 89 immediate and 113 deferred group participants experienced a primary end point (hazard ratio of 0.79 [95% confidence interval, 0.60 to 1.04] versus hazard ratio of 0.47 [95% confidence interval, 0.34 to 0.65; P<0.001]) before 2016 (P=0.02 for hazard ratio difference).Among adults with CD4+ counts >500 cells/mm3, excess risk of AIDS and SNA associated with delaying treatment initiation was diminished after ART initiation, but persistent excess risk remained. (Funded by the National Institute of Allergy and Infectious Diseases and others.).
|
|
| 4. |
-
The Seventeenth Data Release of the Sloan Digital Sky Surveys : Complete Release of MaNGA, MaStar, and APOGEE-2 Data
- 2022
-
Ingår i: Astrophysical Journal Supplement Series. - : Institute of Physics (IOP). - 0067-0049 .- 1538-4365. ; 259:2
-
Tidskriftsartikel (refereegranskat)abstract
- This paper documents the seventeenth data release (DR17) from the Sloan Digital Sky Surveys; the fifth and final release from the fourth phase (SDSS-IV). DR17 contains the complete release of the Mapping Nearby Galaxies at Apache Point Observatory (MaNGA) survey, which reached its goal of surveying over 10,000 nearby galaxies. The complete release of the MaNGA Stellar Library accompanies this data, providing observations of almost 30,000 stars through the MaNGA instrument during bright time. DR17 also contains the complete release of the Apache Point Observatory Galactic Evolution Experiment 2 survey that publicly releases infrared spectra of over 650,000 stars. The main sample from the Extended Baryon Oscillation Spectroscopic Survey (eBOSS), as well as the subsurvey Time Domain Spectroscopic Survey data were fully released in DR16. New single-fiber optical spectroscopy released in DR17 is from the SPectroscipic IDentification of ERosita Survey subsurvey and the eBOSS-RM program. Along with the primary data sets, DR17 includes 25 new or updated value-added catalogs. This paper concludes the release of SDSS-IV survey data. SDSS continues into its fifth phase with observations already underway for the Milky Way Mapper, Local Volume Mapper, and Black Hole Mapper surveys.
|
|
