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- Wang, Anqi, et al.
(författare)
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Characterizing prostate cancer risk through multi-ancestry genome-wide discovery of 187 novel risk variants
- 2023
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 55:12, s. 2065-2074
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Tidskriftsartikel (refereegranskat)abstract
- The transferability and clinical value of genetic risk scores (GRSs) across populations remain limited due to an imbalance in genetic studies across ancestrally diverse populations. Here we conducted a multi-ancestry genome-wide association study of 156,319 prostate cancer cases and 788,443 controls of European, African, Asian and Hispanic men, reflecting a 57% increase in the number of non-European cases over previous prostate cancer genome-wide association studies. We identified 187 novel risk variants for prostate cancer, increasing the total number of risk variants to 451. An externally replicated multi-ancestry GRS was associated with risk that ranged from 1.8 (per standard deviation) in African ancestry men to 2.2 in European ancestry men. The GRS was associated with a greater risk of aggressive versus non-aggressive disease in men of African ancestry (P = 0.03). Our study presents novel prostate cancer susceptibility loci and a GRS with effective risk stratification across ancestry groups.
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- Conti, David, V, et al.
(författare)
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Trans-ancestry genome-wide association meta-analysis of prostate cancer identifies new susceptibility loci and informs genetic risk prediction
- 2021
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Ingår i: Nature Genetics. - : Springer Nature. - 1061-4036 .- 1546-1718. ; 53:1, s. 65-75
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Tidskriftsartikel (refereegranskat)abstract
- Prostate cancer is a highly heritable disease with large disparities in incidence rates across ancestry populations. We conducted a multiancestry meta-analysis of prostate cancer genome-wide association studies (107,247 cases and 127,006 controls) and identified 86 new genetic risk variants independently associated with prostate cancer risk, bringing the total to 269 known risk variants. The top genetic risk score (GRS) decile was associated with odds ratios that ranged from 5.06 (95% confidence interval (CI), 4.84-5.29) for men of European ancestry to 3.74 (95% CI, 3.36-4.17) for men of African ancestry. Men of African ancestry were estimated to have a mean GRS that was 2.18-times higher (95% CI, 2.14-2.22), and men of East Asian ancestry 0.73-times lower (95% CI, 0.71-0.76), than men of European ancestry. These findings support the role of germline variation contributing to population differences in prostate cancer risk, with the GRS offering an approach for personalized risk prediction. A meta-analysis of genome-wide association studies across different populations highlights new risk loci and provides a genetic risk score that can stratify prostate cancer risk across ancestries.
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- Lavesque, N., et al.
(författare)
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The "Spaghetti Project": the final identification guide to European Terebellidae (sensu lato) (Annelida, Terebelliformia)
- 2021
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Ingår i: European Journal of Taxonomy. - : Museum National D'Histoire Naturelle. - 2118-9773. ; 782, s. 108-156
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Tidskriftsartikel (refereegranskat)abstract
- This paper is the conclusion of the "Spaghetti Project" aiming to revise French species of Terebellidae sensu lato (s.l.) belonging to the five families: Polycirridae, Telothelepodidae, Terebellidae sensu stricto (s.s.), Thelepodidae and Trichobranchidae. During this project, 41 species were observed, 31 of them new for science: eight species of Polycirridae, eleven species of Terebellidae s.s., three species of Thelepodidae and nine species of Trichobranchidae. We provide a comprehensive key for all European species of terebellids with a focus on the important diagnostic characters for each family. Finally, we discuss issues on taxonomy, biodiversity and cryptic and pseudo-cryptic species of polychaetes in European waters, based on results obtained during this project.
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- Joseph, A, et al.
(författare)
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Effects of acyl-coenzyme A binding protein (ACBP)/diazepam-binding inhibitor (DBI) on body mass index
- 2021
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Ingår i: Cell death & disease. - : Springer Science and Business Media LLC. - 2041-4889. ; 12:6, s. 599-
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Tidskriftsartikel (refereegranskat)abstract
- In mice, the plasma concentrations of the appetite-stimulatory and autophagy-inhibitory factor acyl-coenzyme A binding protein (ACBP, also called diazepam-binding inhibitor, DBI) acutely increase in response to starvation, but also do so upon chronic overnutrition leading to obesity. Here, we show that knockout of Acbp/Dbi in adipose tissue is sufficient to prevent high-fat diet-induced weight gain in mice. We investigated ACBP/DBI plasma concentrations in several patient cohorts to discover a similar dual pattern of regulation. In relatively healthy subjects, ACBP/DBI concentrations independently correlated with body mass index (BMI) and age. The association between ACBP/DBI and BMI was lost in subjects that underwent major weight gain in the subsequent 3–9 years, as well as in advanced cancer patients. Voluntary fasting, undernutrition in the context of advanced cancer, as well as chemotherapy were associated with an increase in circulating ACBP/DBI levels. Altogether, these results support the conclusion that ACBP/DBI may play an important role in body mass homeostasis as well as in its failure.
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- Schewa, S., et al.
(författare)
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A THz transparent 3D printed microfluidic cell for small angle x-ray scattering
- 2020
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Ingår i: Review of Scientific Instruments. - : AIP Publishing. - 0034-6748 .- 1089-7623. ; 91:8
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Tidskriftsartikel (refereegranskat)abstract
- Excitation frequencies in the terahertz (THz) range are expected to lead to functionally relevant domain movements within the biological macromolecules such as proteins. The possibility of examining such movements in an aqueous environment is particularly valuable since here proteins are not deprived of any motional degrees of freedom. Small angle x-ray scattering (SAXS) is a powerful method to study the structure and domain movements of proteins in solution. Here, we present a microfluidic cell for SAXS experiments, which is also transparent for THz radiation. Specifically, cell dimensions and material were optimized for both radiation sources. In addition, the polystyrene cell can be 3D printed and easily assembled. We demonstrate the practicality of our design for SAXS measurements on several proteins in solution.
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