Institution
Uppsala University
Education•Uppsala, Sweden•
About: Uppsala University is a education organization based out in Uppsala, Sweden. It is known for research contribution in the topics: Population & Gene. The organization has 36485 authors who have published 107509 publications receiving 4220668 citations. The organization is also known as: Uppsala universitet & uu.se.
Topics: Population, Gene, Context (language use), Thin film, Receptor
Papers published on a yearly basis
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University of Oxford1, University of Cambridge2, Imperial College London3, French Alternative Energies and Atomic Energy Commission4, Wellcome Trust Sanger Institute5, Karolinska Institutet6, Karolinska University Hospital7, Uppsala University8, Leibniz Association9, University of Michigan10, Queen Mary University of London11, University of Leicester12, AstraZeneca13, University of Surrey14, University of Helsinki15, University of Amsterdam16, Harokopio University17, McGill University18, McMaster University19
TL;DR: Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD), a modest number considering the apparent heritability of CAD(8) as mentioned in this paper.
Abstract: Genome-wide association studies have identified 11 common variants convincingly associated with coronary artery disease (CAD)(1-7), a modest number considering the apparent heritability of CAD(8). ...
654 citations
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Nasim Mavaddat1, Kyriaki Michailidou2, Kyriaki Michailidou1, Joe Dennis1 +307 more•Institutions (105)
TL;DR: This PRS, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset is developed and empirically validated and is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
Abstract: Stratification of women according to their risk of breast cancer based on polygenic risk scores (PRSs) could improve screening and prevention strategies. Our aim was to develop PRSs, optimized for prediction of estrogen receptor (ER)-specific disease, from the largest available genome-wide association dataset and to empirically validate the PRSs in prospective studies. The development dataset comprised 94,075 case subjects and 75,017 control subjects of European ancestry from 69 studies, divided into training and validation sets. Samples were genotyped using genome-wide arrays, and single-nucleotide polymorphisms (SNPs) were selected by stepwise regression or lasso penalized regression. The best performing PRSs were validated in an independent test set comprising 11,428 case subjects and 18,323 control subjects from 10 prospective studies and 190,040 women from UK Biobank (3,215 incident breast cancers). For the best PRSs (313 SNPs), the odds ratio for overall disease per 1 standard deviation in ten prospective studies was 1.61 (95%CI: 1.57-1.65) with area under receiver-operator curve (AUC) = 0.630 (95%CI: 0.628-0.651). The lifetime risk of overall breast cancer in the top centile of the PRSs was 32.6%. Compared with women in the middle quintile, those in the highest 1% of risk had 4.37- and 2.78-fold risks, and those in the lowest 1% of risk had 0.16- and 0.27-fold risks, of developing ER-positive and ER-negative disease, respectively. Goodness-of-fit tests indicated that this PRS was well calibrated and predicts disease risk accurately in the tails of the distribution. This PRS is a powerful and reliable predictor of breast cancer risk that may improve breast cancer prevention programs.
653 citations
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TL;DR: Among patients with stable angina or an acute coronary syndrome, an iFR‐ guided revascularization strategy was noninferior to an FFR‐guided revascularized strategy with respect to the rate of major adverse cardiac events at 12 months.
Abstract: BackgroundThe instantaneous wave-free ratio (iFR) is an index used to assess the severity of coronary-artery stenosis. The index has been tested against fractional flow reserve (FFR) in small trials, and the two measures have been found to have similar diagnostic accuracy. However, studies of clinical outcomes associated with the use of iFR are lacking. We aimed to evaluate whether iFR is noninferior to FFR with respect to the rate of subsequent major adverse cardiac events. MethodsWe conducted a multicenter, randomized, controlled, open-label clinical trial using the Swedish Coronary Angiography and Angioplasty Registry for enrollment. A total of 2037 participants with stable angina or an acute coronary syndrome who had an indication for physiologically guided assessment of coronary-artery stenosis were randomly assigned to undergo revascularization guided by either iFR or FFR. The primary end point was the rate of a composite of death from any cause, nonfatal myocardial infarction, or unplanned revascul...
652 citations
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TL;DR: How next generation sequencing (NGS) has transformed their ability to identify the genes underpinning adaptation is summarized to demonstrate how the application of these genomic tools to ecological model species means that the authors can start addressing some of the questions that have puzzled ecological geneticists for decades.
Abstract: Understanding the genetics of how organisms adapt to changing environments is a fundamental topic in modern evolutionary ecology. The field is currently progressing rapidly because of advances in genomics technologies, especially DNA sequencing. The aim of this review is to first briefly summarise how next generation sequencing (NGS) has transformed our ability to identify the genes underpinning adaptation. We then demonstrate how the application of these genomic tools to ecological model species means that we can start addressing some of the questions that have puzzled ecological geneticists for decades such as: How many genes are involved in adaptation? What types of genetic variation are responsible for adaptation? Does adaptation utilise pre-existing genetic variation or does it require new mutations to arise following an environmental change?
652 citations
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TL;DR: A commonIRF5 haplotype driving elevated expression of multiple unique isoforms of IRF5 is an important genetic risk factor for SLE, establishing a causal role for type I IFN pathway genes in human autoimmunity.
Abstract: Systemic lupus erythematosus (SLE) is a complex autoimmune disease characterized by activation of the type I interferon (IFN) pathway. Here we convincingly replicate association of the IFN regulatory factor 5 (IRF5) rs2004640 T allele with SLE in four independent case-control cohorts (P = 4.4 x 10(-16)) and by family-based transmission disequilibrium test analysis (P = 0.0006). The rs2004640 T allele creates a 5' donor splice site in an alternate exon 1 of IRF5, allowing expression of several unique IRF5 isoforms. We also identify an independent cis-acting variant associated with elevated expression of IRF5 and linked to the exon 1B splice site. Haplotypes carrying the variant associated with elevated expression and lacking the exon 1B donor site do not confer risk of SLE. Thus, a common IRF5 haplotype driving elevated expression of multiple unique isoforms of IRF5 is an important genetic risk factor for SLE, establishing a causal role for type I IFN pathway genes in human autoimmunity.
652 citations
Authors
Showing all 36854 results
Name | H-index | Papers | Citations |
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Zhong Lin Wang | 245 | 2529 | 259003 |
Lewis C. Cantley | 196 | 748 | 169037 |
Darien Wood | 160 | 2174 | 136596 |
Kaj Blennow | 160 | 1845 | 116237 |
Christopher J. O'Donnell | 159 | 869 | 126278 |
Tomas Hökfelt | 158 | 1033 | 95979 |
Peter G. Schultz | 156 | 893 | 89716 |
Frederik Barkhof | 154 | 1449 | 104982 |
Deepak L. Bhatt | 149 | 1973 | 114652 |
Svante Pääbo | 147 | 407 | 84489 |
Jan-Åke Gustafsson | 147 | 1058 | 98804 |
Hans-Olov Adami | 145 | 908 | 83473 |
Hermann Kolanoski | 145 | 1279 | 96152 |
Kjell Fuxe | 142 | 1479 | 89846 |
Jan Conrad | 141 | 826 | 71445 |