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Träfflista för sökning "WFRF:(Nakanishi T) ;lar1:(umu)"

Sökning: WFRF:(Nakanishi T) > Umeå universitet

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  • Chen, Y. H., et al. (författare)
  • Genomic atlas of the plasma metabolome prioritizes metabolites implicated in human diseases
  • 2023
  • Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 55, s. 44-53
  • Tidskriftsartikel (refereegranskat)abstract
    • Metabolic processes can influence disease risk and provide therapeutic targets. By conducting genome-wide association studies of 1,091 blood metabolites and 309 metabolite ratios, we identified associations with 690 metabolites at 248 loci and associations with 143 metabolite ratios at 69 loci. Integrating metabolite-gene and gene expression information identified 94 effector genes for 109 metabolites and 48 metabolite ratios. Using Mendelian randomization (MR), we identified 22 metabolites and 20 metabolite ratios having estimated causal effect on 12 traits and diseases, including orotate for estimated bone mineral density, alpha-hydroxyisovalerate for body mass index and ergothioneine for inflammatory bowel disease and asthma. We further measured the orotate level in a separate cohort and demonstrated that, consistent with MR, orotate levels were positively associated with incident hip fractures. This study provides a valuable resource describing the genetic architecture of metabolites and delivers insights into their roles in common diseases, thereby offering opportunities for therapeutic targets.
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  • Zhou, Sirui, et al. (författare)
  • A Neanderthal OAS1 isoform protects individuals of European ancestry against COVID-19 susceptibility and severity
  • 2021
  • Ingår i: Nature Medicine. - : Springer Nature. - 1078-8956 .- 1546-170X. ; 27:4, s. 659-667
  • Tidskriftsartikel (refereegranskat)abstract
    • To identify circulating proteins influencing Coronavirus Disease 2019 (COVID-19) susceptibility and severity, we undertook a two-sample Mendelian randomization (MR) study, rapidly scanning hundreds of circulating proteins while reducing bias due to reverse causation and confounding. In up to 14,134 cases and 1.2 million controls, we found that an s.d. increase in OAS1 levels was associated with reduced COVID-19 death or ventilation (odds ratio (OR) = 0.54, P = 7 × 10−8), hospitalization (OR = 0.61, P = 8 × 10−8) and susceptibility (OR = 0.78, P = 8 × 10−6). Measuring OAS1 levels in 504 individuals, we found that higher plasma OAS1 levels in a non-infectious state were associated with reduced COVID-19 susceptibility and severity. Further analyses suggested that a Neanderthal isoform of OAS1 in individuals of European ancestry affords this protection. Thus, evidence from MR and a case–control study support a protective role for OAS1 in COVID-19 adverse outcomes. Available pharmacological agents that increase OAS1 levels could be prioritized for drug development.
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