| 401. |
- Weinhold, Niels, et al.
(författare)
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Inherited genetic susceptibility to monoclonal gammopathy of unknown significance
- 2014
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Ingår i: Blood. - : American Society of Hematology. - 1528-0020 .- 0006-4971. ; 123:16, s. 2513-2517
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Tidskriftsartikel (refereegranskat)abstract
- Monoclonal gammopathy of undetermined significance (MGUS) is present in similar to 2% of individuals age >50 years. The increased risk of multiple myeloma (MM) in relatives of individuals with MGUS is consistent with MGUS being a marker of inherited genetic susceptibility to MM. Common single-nucleotide polymorphisms (SNPs) at 2p23.3 (rs6746082), 3p22.1 (rs1052501), 3q26.2 (rs10936599), 6p21.33 (rs2285803), 7p15.3 (rs4487645), 17p11.2 (rs4273077), and 22q13.1 (rs877529) have recently been shown to influence MM risk. To examine the impact of these 7 SNPs on MGUS, we analyzed two case-control series totaling 492 cases and 7306 controls. Each SNP independently influenced MGUS risk with statistically significant associations (P < .02) for rs1052501, rs2285803, rs4487645, and rs4273077. SNP associations were independent, with risk increasing with a larger number of risk alleles carried (per allele odds ratio, 1.18; P < 10(-7)). Collectively these data are consistent with a polygenic model of disease susceptibility to MGUS.
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| 402. |
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| 403. |
- Went, Molly, et al.
(författare)
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Genetic correlation between multiple myeloma and chronic lymphocytic leukaemia provides evidence for shared aetiology
- 2018
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Ingår i: Blood Cancer Journal. - : Springer Science and Business Media LLC. - 2044-5385. ; 9:1
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Tidskriftsartikel (refereegranskat)abstract
- The clustering of different types of B-cell malignancies in families raises the possibility of shared aetiology. To examine this, we performed cross-trait linkage disequilibrium (LD)-score regression of multiple myeloma (MM) and chronic lymphocytic leukaemia (CLL) genome-wide association study (GWAS) data sets, totalling 11,734 cases and 29,468 controls. A significant genetic correlation between these two B-cell malignancies was shown (Rg = 0.4, P = 0.0046). Furthermore, four of the 45 known CLL risk loci were shown to associate with MM risk and five of the 23 known MM risk loci associate with CLL risk. By integrating eQTL, Hi-C and ChIP-seq data, we show that these pleiotropic risk loci are enriched for B-cell regulatory elements and implicate B-cell developmental genes. These data identify shared biological pathways influencing the development of CLL and, MM and further our understanding of the aetiological basis of these B-cell malignancies.
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| 404. |
- Willer, Cristen J., et al.
(författare)
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Discovery and refinement of loci associated with lipid levels
- 2013
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 45:11, s. 1274-1283
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Tidskriftsartikel (refereegranskat)abstract
- Levels of low-density lipoprotein (LDL) cholesterol, high-density lipoprotein (HDL) cholesterol, triglycerides and total cholesterol are heritable, modifiable risk factors for coronary artery disease. To identify new loci and refine known loci influencing these lipids, we examined 188,577 individuals using genome-wide and custom genotyping arrays. We identify and annotate 157 loci associated with lipid levels at P < 5 x 10(-8), including 62 loci not previously associated with lipid levels in humans. Using dense genotyping in individuals of European, East Asian, South Asian and African ancestry, we narrow association signals in 12 loci. We find that loci associated with blood lipid levels are often associated with cardiovascular and metabolic traits, including coronary artery disease, type 2 diabetes, blood pressure, waist-hip ratio and body mass index. Our results demonstrate the value of using genetic data from individuals of diverse ancestry and provide insights into the biological mechanisms regulating blood lipids to guide future genetic, biological and therapeutic research.
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| 405. |
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| 406. |
- Zhao, Chaoyang, et al.
(författare)
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A massive expansion of effector genes underlies gall-formation in the wheat pest Mayetiola destructor
- 2015
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Ingår i: Current Biology. - : Elsevier BV. - 1879-0445 .- 0960-9822. ; 25:5, s. 613-620
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Tidskriftsartikel (refereegranskat)abstract
- Gall-forming arthropods are highly specialized herbivores that, in combination with their hosts, produce extended phenotypes with unique morphologies [1]. Many are economically important, and others have improved our understanding of ecology and adaptive radiation [2]. However, the mechanisms that these arthropods use to induce plant galls are poorly understood. We sequenced the genome of the Hessian fly (Mayetiola destructor; Diptera: Cecidomyiidae), a plant parasitic gall midge and a pest of wheat (Triticum spp.), with the aim of identifying genic modifications that contribute to its plant-parasitic lifestyle. Among several adaptive modifications, we discovered an expansive reservoir of potential effector proteins. Nearly 5% of the 20,163 predicted gene models matched putative effector gene transcripts present in the M. destructor larval salivary gland. Another 466 putative effectors were discovered among the genes that have no sequence similarities in other organisms. The largest known arthropod gene family (family SSGP-71) was also discovered within the effector reservoir. SSGP-71 proteins lack sequence homologies to other proteins, but their structures resemble both ubiquitin E3 ligases in plants and E3-ligase-mimicking effectors in plant pathogenic bacteria. SSGP-71 proteins and wheat Skp proteins interact in vivo. Mutations in different SSGP-71 genes avoid the effector-triggered immunity that is directed by the wheat resistance genes H6 and H9. Results point to effectors as the agents responsible for arthropod-induced plant gall formation.
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| 407. |
- Baer, David J, et al.
(författare)
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Targeting the Dietary Na : K Ratio-Considerations for Design of an Intervention Study to Impact Blood Pressure.
- 2021
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Ingår i: Advances in nutrition (Bethesda, Md.). - : Oxford University Press. - 2156-5376 .- 2161-8313. ; 13:1, s. 225-233
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Tidskriftsartikel (refereegranskat)abstract
- Despite medical, dietary, and lifestyle recommendations and drug advancements, hypertension persists as among the most prevalent noncommunicable diseases in the US population, and control remains elusive. Uncontrolled hypertension may increase the risk of serious illness from various other health challenges, including cardiovascular and renal responses. Adoption of a healthy diet is a consistent core element of lifestyle modifications that are recommended for mitigation of hypertension. The dietary sodium-to-potassium ratio is recognized as having promising potential in the regulation of blood pressure. In fact, the understanding of the relation between this ratio and blood pressure was documented as a key evidence gap in the 2019 National Academies of Sciences, Engineering, and Medicine report that revised recommended intake levels for both sodium and potassium. Although notable animal and human evidence supports this point, fundamental to developing a specific dietary recommendation for a sodium-to-potassium ratio is a well-designed human intervention trial. The successful translatability of such a trial will require careful consideration of study elements, including the study population, duration, blood pressure measurement, and dietary intervention, among other factors. This paper addresses these decision points and serves as supporting documentation for a research group or organization with the interest and means to address this important data gap, which will undoubtedly be foundational for advancing dietary guidance and would inform the next iteration of Dietary Reference Intakes for sodium and potassium.
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| 408. |
- Barragán, O., et al.
(författare)
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K2-141 b: A 5-M⊕ super-Earth transiting a K7 V star every 6.7 hours
- 2018
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 612
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Tidskriftsartikel (refereegranskat)abstract
- We report on the discovery of K2-141 b (EPIC 246393474 b), an ultra-short-period super-Earth on a 6.7 h orbit transiting an active K7 V star based on data from K2 campaign 12. We confirmed the planet's existence and measured its mass with a series of follow-up observations: seeing-limited Muscat imaging, NESSI high-resolution speckle observations, and FIES and HARPS high-precision radial-velocity monitoring. K2-141 b has a mass of 5.31 ± 0.46 M ⊗ and radius of 1.54 -0.09 +0.10 R ⊗ , yielding a mean density of 8.00 -1.45 +1.83 g cm -3 and suggesting a rocky-iron composition. Models indicate that iron cannot exceed ∼70% of the total mass. With an orbital period of only 6.7 h, K2-141 b is the shortest-period planet known to date with a precisely determined mass.
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| 409. |
- Baxter, Amanda L., et al.
(författare)
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Collaborative experience between scientific software projects using Agile Scrum development
- 2022
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Ingår i: Software, practice & experience. - : John Wiley & Sons. - 0038-0644 .- 1097-024X. ; 52:10, s. 2077-2096
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Tidskriftsartikel (refereegranskat)abstract
- Developing sustainable software for the scientific community requires expertise in software engineering and domain science. This can be challenging due to the unique needs of scientific software, the insufficient resources for software engineering practices in the scientific community, and the complexity of developing for evolving scientific contexts. While open-source software can partially address these concerns, it can introduce complicating dependencies and delay development. These issues can be reduced if scientists and software developers collaborate. We present a case study wherein scientists from the SuperNova Early Warning System collaborated with software developers from the Scalable Cyberinfrastructure for Multi-Messenger Astrophysics project. The collaboration addressed the difficulties of open-source software development, but presented additional risks to each team. For the scientists, there was a concern of relying on external systems and lacking control in the development process. For the developers, there was a risk in supporting a user-group while maintaining core development. These issues were mitigated by creating a second Agile Scrum framework in parallel with the developers' ongoing Agile Scrum process. This Agile collaboration promoted communication, ensured that the scientists had an active role in development, and allowed the developers to evaluate and implement the scientists' software requirements. The collaboration provided benefits for each group: the scientists actuated their development by using an existing platform, and the developers utilized the scientists' use-case to improve their systems. This case study suggests that scientists and software developers can avoid scientific computing issues by collaborating and that Agile Scrum methods can address emergent concerns.
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| 410. |
- Broderick, Peter, et al.
(författare)
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Common variation at 3p22.1 and 7p15.3 influences multiple myeloma risk
- 2012
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Ingår i: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 44:1, s. 58-83
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Tidskriftsartikel (refereegranskat)abstract
- To identify risk variants for multiple myeloma, we conducted a genome-wide association study of 1,675 individuals with multiple myeloma and 5,903 control subjects. We identified risk loci for multiple myeloma at 3p22.1 (rs1052501 in ULK4; odds ratio (OR) = 1.32; P = 7.47 x 10(-9)) and 7p15.3 (rs4487645, OR = 1.38; P = 3.33 x 10(-15)). In addition, we observed a promising association at 2p23.3 (rs6746082, OR = 1.29; P = 1.22 x 10(-7)). Our study identifies new genomic regions associated with multiple myeloma risk that may lead to new etiological insights.
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