| 11. |
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| 12. |
- Kraja, Aldi T., et al.
(författare)
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New Blood Pressure-Associated Loci Identified in Meta-Analyses of 475000 Individuals
- 2017
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Ingår i: Circulation. - : LIPPINCOTT WILLIAMS & WILKINS. - 1942-325X .- 1942-3268. ; 10:5
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Tidskriftsartikel (refereegranskat)abstract
- Background - Genome-wide association studies have recently identified >400 loci that harbor DNA sequence variants that influence blood pressure (BP). Our earlier studies identified and validated 56 single nucleotide variants (SNVs) associated with BP from meta-analyses of exome chip genotype data. An additional 100 variants yielded suggestive evidence of association.Methods and Results - Here, we augment the sample with 140886 European individuals from the UK Biobank, in whom 77 of the 100 suggestive SNVs were available for association analysis with systolic BP or diastolic BP or pulse pressure. We performed 2 meta-analyses, one in individuals of European, South Asian, African, and Hispanic descent (pan-ancestry, approximate to 475000), and the other in the subset of individuals of European descent (approximate to 423000). Twenty-one SNVs were genome-wide significant (P<5x10(-8) ) for BP, of which 4 are new BP loci: rs9678851 (missense, SLC4A1AP), rs7437940 (AFAP1), rs13303 (missense, STAB1), and rs1055144 (7p15.2). In addition, we identified a potentially independent novel BP-associated SNV, rs3416322 (missense, SYNPO2L) at a known locus, uncorrelated with the previously reported SNVs. Two SNVs are associated with expression levels of nearby genes, and SNVs at 3 loci are associated with other traits. One SNV with a minor allele frequency <0.01, (rs3025380 at DBH) was genome-wide significant.Conclusions - We report 4 novel loci associated with BP regulation, and 1 independent variant at an established BP locus. This analysis highlights several candidate genes with variation that alter protein function or gene expression for potential follow-up.
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| 13. |
- Li, Man, et al.
(författare)
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SOS2 and ACP1 Loci Identified through Large-Scale Exome Chip Analysis Regulate Kidney Development and Function
- 2017
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Ingår i: Journal of the American Society of Nephrology: JASN. - 1533-3450. ; 28:3, s. 981-994
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Tidskriftsartikel (refereegranskat)abstract
- Genome-wide association studies have identified >50 common variants associated with kidney function, but these variants do not fully explain the variation in eGFR. We performed a two-stage meta-analysis of associations between genotypes from the Illumina exome array and eGFR on the basis of serum creatinine (eGFRcrea) among participants of European ancestry from the CKDGen Consortium (nStage1: 111,666; nStage2: 48,343). In single-variant analyses, we identified single nucleotide polymorphisms at seven new loci associated with eGFRcrea (PPM1J, EDEM3, ACP1, SPEG, EYA4, CYP1A1, and ATXN2L; PStage1<3.7×10-7), of which most were common and annotated as nonsynonymous variants. Gene-based analysis identified associations of functional rare variants in three genes with eGFRcrea, including a novel association with the SOS Ras/Rho guanine nucleotide exchange factor 2 gene, SOS2 (P=5.4×10-8 by sequence kernel association test). Experimental follow-up in zebrafish embryos revealed changes in glomerular gene expression and renal tubule morphology in the embryonic kidney of acp1- and sos2-knockdowns. These developmental abnormalities associated with altered blood clearance rate and heightened prevalence of edema. This study expands the number of loci associated with kidney function and identifies novel genes with potential roles in kidney formation.
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| 14. |
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| 15. |
- Mahajan, Anubha, et al.
(författare)
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Refining the accuracy of validated target identification through coding variant fine-mapping in type 2 diabetes
- 2018
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Ingår i: Nature Genetics. - : Nature Publishing Group. - 1061-4036 .- 1546-1718. ; 50:4, s. 559-571
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Tidskriftsartikel (refereegranskat)abstract
- We aggregated coding variant data for 81,412 type 2 diabetes cases and 370,832 controls of diverse ancestry, identifying 40 coding variant association signals (P < 2.2 × 10−7); of these, 16 map outside known risk-associated loci. We make two important observations. First, only five of these signals are driven by low-frequency variants: even for these, effect sizes are modest (odds ratio ≤1.29). Second, when we used large-scale genome-wide association data to fine-map the associated variants in their regional context, accounting for the global enrichment of complex trait associations in coding sequence, compelling evidence for coding variant causality was obtained for only 16 signals. At 13 others, the associated coding variants clearly represent ‘false leads’ with potential to generate erroneous mechanistic inference. Coding variant associations offer a direct route to biological insight for complex diseases and identification of validated therapeutic targets; however, appropriate mechanistic inference requires careful specification of their causal contribution to disease predisposition.
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| 16. |
- Malerba, Franco, et al.
(författare)
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Conceptualizing Knowledge Intensive Entrepreneurship: Definition and Model
- 2016
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Ingår i: Dynamics of knowledge intensive entrepreneurship business strategy & public policy edited by Franco Malerba, Yannis Caloghirou, Maureen McKelvey, Slavo Radosevic.. - United Kingdom : Routledge. - 9781138025288 ; , s. 19-47
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Bokkapitel (refereegranskat)abstract
- Knowledge intensive entrepreneurship (KIE) helps renew the economy, giving rise to new industries but also to entrepreneurial-driven renewal within existing industries. This chapter proposes a conceptualize KIE as a broad concept, including a definition and a model. This chapter examines specific aspects of knowledge intensive entrepreneurship, presenting a conceptualization. The chapter also discusses framework how to operationalize the dimensions of the definition through various research strategies, and explains how the AEGIS project did so. Knowledge-intensive entrepreneurship is considered a key socio-economic phenomenon that drives innovation, and economic growth, and is at the base of the competitiveness of countries.
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| 17. |
- Malerba, Franco, et al.
(författare)
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Conceptualizing Knowledge Intensive Entrepreneurship: Definition and Model
- 2015
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Ingår i: Dynamics of knowledge intensive entrepreneurship business strategy & public policy edited by Franco Malerba, Yannis Caloghirou, Maureen McKelvey, Slavo Radosevic.. - 9781138025288 ; , s. 19-47
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- Knowledge intensive entrepreneurship (KIE) helps renew the economy, giving rise to new industries but also to entrepreneurial-driven renewal within existing industries. This chapter proposes a conceptualize KIE as a broad concept, including a definition and a model. This chapter examines specific aspects of knowledge intensive entrepreneurship, presenting a conceptualization. The chapter also discusses framework how to operationalize the dimensions of the definition through various research strategies, and explains how the AEGIS project did so. Knowledge-intensive entrepreneurship is considered a key socio-economic phenomenon that drives innovation, and economic growth, and is at the base of the competitiveness of countries.
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| 18. |
- Malerba, Franco, et al.
(författare)
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Introduction to the Dynamics of Knowledge Intensive Entrepreneurship
- 2016
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Ingår i: Dynamics of knowledge intensive entrepreneurship business strategy & public policy edited by Franco Malerba, Yannis Caloghirou, Maureen McKelvey, Slavo Radosevic.. - United Kingdom : Routledge. - 9781138025288
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Bokkapitel (refereegranskat)abstract
- This chapter introduces the concept of Knowledge Intensive Entrepreneurship. Moreover, the chapter positions this concept, by providing an overview of previous research, as well as chapters in this book.
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| 19. |
- Malerba, Franco, et al.
(författare)
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Introduction to the Dynamics of Knowledge Intensive Entrepreneurship
- 2015
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Ingår i: Dynamics of Knowledge Intensive Entrepreneurship: Business Strategy and Public Policy / Edited by Franco Malerba, Yannis Caloghirou, Maureen McKelvey, Slavo Radoševic. - 9781138025288
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Bokkapitel (övrigt vetenskapligt/konstnärligt)abstract
- This chapter introduces the concept of Knowledge Intensive Entrepreneurship. Moreover, the chapter positions this concept, by providing an overview of previous research, as well as chapters in this book.
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| 20. |
- Malerba, Franco, et al.
(författare)
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Knowledge Intensive Entrepreneurship and Future Research Directions
- 2016
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Ingår i: International Joseph Schumpeter Society Conference, June 2016, Montreal.
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Konferensbidrag (övrigt vetenskapligt/konstnärligt)abstract
- The paper focuses upon a particular type of entrepreneurship, namely knowledge intensive entrepreneurship (KIE) and future research trajectories. Our approach follows a Schumpeterian approach, in the sense that entrepreneurship is driven by the innovation and the activities of entrepreneurs, who are responding to opportunities in markets and technology. Moreover, entrepreneurial activities introduce uncertainty and disequilibrium into the economy, which in turn promote economic development. More specifically, this paper focuses upon the particular case where advanced knowledge and innovation are the basis of competitive advantage for entrepreneurs. We propose that KIE firms, which introduce innovation and disequilibrium in the economy and rely upon advanced knowledge, can be identified across all types of manufacturing and service sectors, and they do so by taking advantage of diverse innovative opportunities. Hence, the purpose of this paper is to expand the discussion of how to conceptualize the existence, and importance of, knowledge intensive entrepreneurship in order to propose directions for future research, in terms of indicators, measurements and interesting topics.
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