| 1. |
- van de Vegte, Yordi, et al.
(author)
-
Genetic insights into resting heart rate and its role in cardiovascular disease
- 2023
-
In: Nature Communications. - : Springer Nature. - 2041-1723. ; 14:1
-
Journal article (peer-reviewed)abstract
- The genetics and clinical consequences of resting heart rate (RHR) remain incompletely understood. Here, the authors discover new genetic variants associated with RHR and find that higher genetically predicted RHR decreases risk of atrial fibrillation and ischemic stroke. Resting heart rate is associated with cardiovascular diseases and mortality in observational and Mendelian randomization studies. The aims of this study are to extend the number of resting heart rate associated genetic variants and to obtain further insights in resting heart rate biology and its clinical consequences. A genome-wide meta-analysis of 100 studies in up to 835,465 individuals reveals 493 independent genetic variants in 352 loci, including 68 genetic variants outside previously identified resting heart rate associated loci. We prioritize 670 genes and in silico annotations point to their enrichment in cardiomyocytes and provide insights in their ECG signature. Two-sample Mendelian randomization analyses indicate that higher genetically predicted resting heart rate increases risk of dilated cardiomyopathy, but decreases risk of developing atrial fibrillation, ischemic stroke, and cardio-embolic stroke. We do not find evidence for a linear or non-linear genetic association between resting heart rate and all-cause mortality in contrast to our previous Mendelian randomization study. Systematic alteration of key differences between the current and previous Mendelian randomization study indicates that the most likely cause of the discrepancy between these studies arises from false positive findings in previous one-sample MR analyses caused by weak-instrument bias at lower P-value thresholds. The results extend our understanding of resting heart rate biology and give additional insights in its role in cardiovascular disease development.
|
|
| 2. |
|
|
| 3. |
- Ihre, Johan, 1707-1780
(author)
-
Dissertatio posterior, nexum gloriæ dei cum utilitate humana sistens, quam, ex consensu ampliss. Facult. Philosoph. in Regia Academia Upsaliensi, præside, ... Johanne Ihre, ... pro gradu, publico examini modeste subjicit Laurentius Kraft, Ol. Fil. Arosia-Westmannus. In Auditorio [Carolino Majori] ad diem 31. Maji, Anni MDCCXLVI. Horis, ante meridiem, consuetis.
- 1746
-
Doctoral thesis (other academic/artistic)
|
|
| 4. |
- Ihre, Johan, 1707-1780
(author)
-
Dissertatio prior, nexum gloriæ dei cum utilitate humana sistens, quam, ex consensu ampliss. Facult. Philosoph. in Regia Academia Upsaliensi, præside, ... Johanne Ihre, ... publico examini modeste subjicit Laurentius Kraft, Ol. Fil. Arosia-Westmannus. In Auditorio Carolino Majori, ad d. XVII. Aprilis anni MDCCXLV. Horis, ante meridiem, consuetis.
- 1745
-
Doctoral thesis (other academic/artistic)
|
|
| 5. |
- Sleincour, Johan Peter, 1714-1785
(author)
-
Dissertatio philosophica, de interna, cum bene faciendi studio, conjuncta delectatione, quam, consensu ampliss. facult. philosoph. reg. acad. upsal. præside Mag. Joh. Petro Sleincour, ... Petrus L. Kraft, Dalekarlus. In aud. Carol. majori die VIII Maji, MDCCLXXVI.
- 1776
-
Doctoral thesis (other academic/artistic)
|
|
| 6. |
|
|
| 7. |
- Bohlin, Markus, et al.
(author)
-
Simulation-Based Timing Analysis of Complex Real-Time Systems
- 2009
-
In: 2009 15TH IEEE INTERNATIONAL CONFERENCE ON EMBEDDED AND REAL-TIME COMPUTING SYSTEMS AND APPLICATIONS, PROCEEDINGS. - 9780769537870 ; , s. 321-328
-
Conference paper (peer-reviewed)abstract
- This paper presents an efficient best-effort approach for simulation-based timing analysis of complex real- time systems. The method can handle in principle any software design that can be simulated, and is based on controlling simulation input using a simple yet novel hill- climbing algorithm. Unlike previous approaches, the new algorithm directly manipulates simulation parameters such as execution times, arrival jitter and input. An evaluation is presented using six different simulation models, and two other simulation methods as reference: Monte Carlo simulation and MABERA. The new method proposed in this paper was 4-11% more accurate while at the same time 42 times faster, on average, than the reference methods.
|
|
| 8. |
- Elks, Cathy E, et al.
(author)
-
Thirty new loci for age at menarche identified by a meta-analysis of genome-wide association studies
- 2010
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1061-4036 .- 1546-1718. ; 42:12, s. 1077-85
-
Journal article (peer-reviewed)abstract
- To identify loci for age at menarche, we performed a meta-analysis of 32 genome-wide association studies in 87,802 women of European descent, with replication in up to 14,731 women. In addition to the known loci at LIN28B (P = 5.4 × 10⁻⁶⁰) and 9q31.2 (P = 2.2 × 10⁻³³), we identified 30 new menarche loci (all P < 5 × 10⁻⁸) and found suggestive evidence for a further 10 loci (P < 1.9 × 10⁻⁶). The new loci included four previously associated with body mass index (in or near FTO, SEC16B, TRA2B and TMEM18), three in or near other genes implicated in energy homeostasis (BSX, CRTC1 and MCHR2) and three in or near genes implicated in hormonal regulation (INHBA, PCSK2 and RXRG). Ingenuity and gene-set enrichment pathway analyses identified coenzyme A and fatty acid biosynthesis as biological processes related to menarche timing.
|
|
| 9. |
- Frazier-Wood, Alexis C., et al.
(author)
-
Genetic variants associated with subjective well-being, depressive symptoms, and neuroticism identified through genome-wide analyses
- 2016
-
In: Nature Genetics. - : Nature Research (part of Springer Nature). - 1061-4036 .- 1546-1718. ; 48, s. 624-
-
Journal article (peer-reviewed)abstract
- Very few genetic variants have been associated with depression and neuroticism, likely because of limitations on sample size in previous studies. Subjective well-being, a phenotype that is genetically correlated with both of these traits, has not yet been studied with genome-wide data. We conducted genome-wide association studies of three phenotypes: subjective well-being (n = 298,420), depressive symptoms (n = 161,460), and neuroticism (n = 170,911). We identify 3 variants associated with subjective well-being, 2 variants associated with depressive symptoms, and 11 variants associated with neuroticism, including 2 inversion polymorphisms. The two loci associated with depressive symptoms replicate in an independent depression sample. Joint analyses that exploit the high genetic correlations between the phenotypes (vertical bar(p) over cap vertical bar approximate to 0.8) strengthen the overall credibility of the findings and allow us to identify additional variants. Across our phenotypes, loci regulating expression in central nervous system and adrenal or pancreas tissues are strongly enriched for association.
|
|
| 10. |
- Gaulton, Kyle J, et al.
(author)
-
Genetic fine mapping and genomic annotation defines causal mechanisms at type 2 diabetes susceptibility loci.
- 2015
-
In: Nature Genetics. - : Springer Science and Business Media LLC. - 1546-1718 .- 1061-4036. ; 47:12, s. 1415-1415
-
Journal article (peer-reviewed)abstract
- We performed fine mapping of 39 established type 2 diabetes (T2D) loci in 27,206 cases and 57,574 controls of European ancestry. We identified 49 distinct association signals at these loci, including five mapping in or near KCNQ1. 'Credible sets' of the variants most likely to drive each distinct signal mapped predominantly to noncoding sequence, implying that association with T2D is mediated through gene regulation. Credible set variants were enriched for overlap with FOXA2 chromatin immunoprecipitation binding sites in human islet and liver cells, including at MTNR1B, where fine mapping implicated rs10830963 as driving T2D association. We confirmed that the T2D risk allele for this SNP increases FOXA2-bound enhancer activity in islet- and liver-derived cells. We observed allele-specific differences in NEUROD1 binding in islet-derived cells, consistent with evidence that the T2D risk allele increases islet MTNR1B expression. Our study demonstrates how integration of genetic and genomic information can define molecular mechanisms through which variants underlying association signals exert their effects on disease.
|
|
