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- Ntalla, Ioanna, et al.
(författare)
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Multi-ancestry GWAS of the electrocardiographic PR interval identifies 202 loci underlying cardiac conduction
- 2020
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Ingår i: Nature Communications. - : Springer Science and Business Media LLC. - 2041-1723. ; 11:1
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Tidskriftsartikel (refereegranskat)abstract
- The electrocardiographic PR interval reflects atrioventricular conduction, and is associated with conduction abnormalities, pacemaker implantation, atrial fibrillation (AF), and cardiovascular mortality. Here we report a multi-ancestry (N=293,051) genome-wide association meta-analysis for the PR interval, discovering 202 loci of which 141 have not previously been reported. Variants at identified loci increase the percentage of heritability explained, from 33.5% to 62.6%. We observe enrichment for cardiac muscle developmental/contractile and cytoskeletal genes, highlighting key regulation processes for atrioventricular conduction. Additionally, 8 loci not previously reported harbor genes underlying inherited arrhythmic syndromes and/or cardiomyopathies suggesting a role for these genes in cardiovascular pathology in the general population. We show that polygenic predisposition to PR interval duration is an endophenotype for cardiovascular disease, including distal conduction disease, AF, and atrioventricular pre-excitation. These findings advance our understanding of the polygenic basis of cardiac conduction, and the genetic relationship between PR interval duration and cardiovascular disease. On the electrocardiogram, the PR interval reflects conduction from the atria to ventricles and also serves as risk indicator of cardiovascular morbidity and mortality. Here, the authors perform genome-wide meta-analyses for PR interval in multiple ancestries and identify 141 previously unreported genetic loci.
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| 2. |
- Olsson, Mikael, 1966-
(författare)
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Ownership reform and corporate governance : The Slovak privatisation process in 1990-1996
- 1999
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Doktorsavhandling (övrigt vetenskapligt/konstnärligt)abstract
- Since 1989, there has been a period of rapid change of the economies of the former Eastern bloc. Within a few years, the majority of the formerly centrally administered economies had begun restructuring their economic systems, including the privatisation. of formerly state-owned enterprises. This process developed differently in different countries, depending among other things on their historical traditions and the momentum of their social, political and economic transformations. This doctoral dissertation examines the privatisation of large-scale industrial enterprises in Slovakia prior to 1997. In particular the thesis analyses the changing political and institutional framework governing the process and method of privatisation; and how the governance of firms was affected by the new markets and ownership- and control-structures that were established. Special attention is paid to the role played by investment funds andinvestment-companies established as a consequence of voucher privatisation. The research problem is approached both from an aggregate national level and from the enterprise level. The thesis includes a number of case studies of enterprises in Slovakia that underwent privatisation, and of investment funds that emerged to take part in the process. In addition, two panel-data sets were constructed for the sake of statistical analysis. The study points to the drastic changes in privatisation policy and its enactment, under different governments. It leads to the conclusion that privatisation is a highly political process, whose economic effects cannot be separated from its distributional effects. This politicised nature of ownership reform is shown to have some negative side-effects with regard to the development of well-functioning governance structures. It is, for example, pointed to that the capital market, as it developed during the period of study, was highly non-transparent,characterised by high transaction costs and insider-trading. The study also documents an increasingly concentrated ownership structure of the Slovak industry and relates it to the changes in privatisation policy. In the final analysis attention is drawn to a recurring theme in the study, namely the issues related to the relative stability and durability of the institutional set-up. In many cases an insecurity about "the rules of the game" led to short-term incentives and opportunism on behalf of the economic and political agents.
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