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- Pulit, S. L., et al.
(författare)
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Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes
- 2018
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Ingår i: Neurology-Genetics. - : Ovid Technologies (Wolters Kluwer Health). - 2376-7839. ; 4:6
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Tidskriftsartikel (refereegranskat)abstract
- Objective We sought to assess whether genetic risk factors for atrial fibrillation (AF) can explain cardioembolic stroke risk. We evaluated genetic correlations between a previous genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors. We observed a strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson r = 0.77 and 0.76, respectively, across SNPs with p < 4.4 x 10(-4) in the previous AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio [OR] per SD = 1.40, p = 1.45 x 10(-48)), explaining similar to 20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per SD = 1.07,p = 0.004), but no other primary stroke subtypes (all p > 0.1). Genetic risk of AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.
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| 2. |
- Marini, S., et al.
(författare)
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Association of Apolipoprotein E With Intracerebral Hemorrhage Risk by Race/Ethnicity A Meta-analysis
- 2019
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Ingår i: Jama Neurology. - : American Medical Association (AMA). - 2168-6149 .- 2168-6157. ; 76:4, s. 480-491
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Tidskriftsartikel (refereegranskat)abstract
- IMPORTANCE Genetic studies of intracerebral hemorrhage (ICH) have focused mainly on white participants, but genetic risk may vary or could be concealed by differing nongenetic coexposures in nonwhite populations. Transethnic analysis of risk may clarify the role of genetics in ICH risk across populations. OBJECTIVE To evaluate associations between established differences in ICH risk by race/ethnicity and the variability in the risks of apolipoprotein E (APOE) epsilon 4 alleles, the most potent genetic risk factor for ICH. DESIGN, SETTING, AND PARTICIPANTS This case-control study of primary ICH meta-analyzed the association of APOE allele status on ICH risk, applying a 2-stage clustering approach based on race/ethnicity and stratified by a contributing study. A propensity score analysis was used to model the association of APOE with the burden of hypertension across race/ethnic groups. Primary ICH cases and controls were collected from 3 hospital- and population-based studies in the United States and 8 in European sites in the International Stroke Genetic Consortium. Participants were enrolled from January 1, 1999, to December 31, 2017. Participants with secondary causes of ICH were excluded from enrollment. Controls were regionally matched within each participating study. MAIN OUTCOMES AND MEASURES Clinical variables were systematically obtained from structured interviews within each site. APOE genotype was centrally determined for all studies. RESULTS In total, 13 124 participants (7153 [54.5%] male with a median [interquartile range] age of 66 [56-76] years) were included. In white participants, APOE epsilon 2 (odds ratio [OR], 1.49; 95% CI, 1.24-1.80; P < .001) and APOE epsilon 4 (OR, 1.51; 95% CI, 1.23-1.85; P < .001) were associated with lobar ICH risk; however, within self-identified Hispanic and black participants, no associations were found. After propensity score matching for hypertension burden, APOE epsilon 4 was associated with lobar ICH risk among Hispanic (OR, 1.14; 95% CI, 1.03-1.28; P = .01) but not in black (OR, 1.02; 95% CI, 0.98-1.07; P = .25) participants. APOE epsilon 2 and epsilon 4 did not show an association with nonlobar ICH risk in any race/ethnicity. CONCLUSIONS AND RELEVANCE APOE epsilon 4 and epsilon 2 alleles appear to affect lobar ICH risk variably by race/ethnicity, associations that are confirmed in white individuals but can be shown in Hispanic individuals only when the excess burden of hypertension is propensity score-matched; further studies are needed to explore the interactions between APOE alleles and environmental exposures that vary by race/ethnicity in representative populations at risk for ICH.
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| 4. |
- Ebersole, Charles R., et al.
(författare)
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Many Labs 5: Testing Pre-Data-Collection Peer Review as an Intervention to Increase Replicability
- 2020
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Ingår i: Advances in Methods and Practices in Psychological Science. - : Sage. - 2515-2467 .- 2515-2459. ; 3:3, s. 309-331
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Tidskriftsartikel (refereegranskat)abstract
- Replication studies in psychological science sometimes fail to reproduce prior findings. If these studies use methods that are unfaithful to the original study or ineffective in eliciting the phenomenon of interest, then a failure to replicate may be a failure of the protocol rather than a challenge to the original finding. Formal pre-data-collection peer review by experts may address shortcomings and increase replicability rates. We selected 10 replication studies from the Reproducibility Project: Psychology (RP:P; Open Science Collaboration, 2015) for which the original authors had expressed concerns about the replication designs before data collection; only one of these studies had yielded a statistically significant effect (p < .05). Commenters suggested that lack of adherence to expert review and low-powered tests were the reasons that most of these RP:P studies failed to replicate the original effects. We revised the replication protocols and received formal peer review prior to conducting new replication studies. We administered the RP:P and revised protocols in multiple laboratories (median number of laboratories per original study = 6.5, range = 3-9; median total sample = 1,279.5, range = 276-3,512) for high-powered tests of each original finding with both protocols. Overall, following the preregistered analysis plan, we found that the revised protocols produced effect sizes similar to those of the RP:P protocols (Delta r = .002 or .014, depending on analytic approach). The median effect size for the revised protocols (r = .05) was similar to that of the RP:P protocols (r = .04) and the original RP:P replications (r = .11), and smaller than that of the original studies (r = .37). Analysis of the cumulative evidence across the original studies and the corresponding three replication attempts provided very precise estimates of the 10 tested effects and indicated that their effect sizes (median r = .07, range = .00-.15) were 78% smaller, on average, than the original effect sizes (median r = .37, range = .19-.50).
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| 5. |
- Luque, R., et al.
(författare)
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A planetary system with two transiting mini-Neptunes near the radius valley transition around the bright M dwarf TOI-776
- 2021
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Ingår i: Astronomy and Astrophysics. - : EDP Sciences. - 0004-6361 .- 1432-0746. ; 645
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Tidskriftsartikel (refereegranskat)abstract
- We report the discovery and characterization of two transiting planets around the bright M1 V star LP 961-53 (TOI-776, J = 8.5 mag, M = 0.54 ± 0.03 M⊙) detected during Sector 10 observations of the Transiting Exoplanet Survey Satellite (TESS). Combining the TESS photometry with HARPS radial velocities, as well as ground-based follow-up transit observations from the MEarth and LCOGT telescopes, for the inner planet, TOI-776 b, we measured a period of Pb = 8.25 d, a radius of Rb = 1.85 ± 0.13 R⊙, and a mass of Mb = 4.0 ± 0.9 M⊙; and for the outer planet, TOI-776 c, a period of Pc = 15.66 d, a radius of Rc = 2.02 ± 0.14 R⊙, and a mass of Mc = 5.3 ± 1.8 M⊙. The Doppler data shows one additional signal, with a period of ~34 d, associated with the rotational period of the star. The analysis of fifteen years of ground-based photometric monitoring data and the inspection of different spectral line indicators confirm this assumption. The bulk densities of TOI-776 b and c allow for a wide range of possible interior and atmospheric compositions. However, both planets have retained a significant atmosphere, with slightly different envelope mass fractions. Thanks to their location near the radius gap for M dwarfs, we can start to explore the mechanism(s) responsible for the radius valley emergence around low-mass stars as compared to solar-like stars. While a larger sample of well-characterized planets in this parameter space is still needed to draw firm conclusions, we tentatively estimate that the stellar mass below which thermally-driven mass loss is no longer the main formation pathway for sculpting the radius valley is between 0.63 and 0.54 M⊙. Due to the brightness of the star, the TOI-776 system is also an excellent target for the James Webb Space Telescope, providing a remarkable laboratory in which to break the degeneracy in planetary interior models and to test formation and evolution theories of small planets around low-mass stars.
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| 7. |
- Hardwicke, Tom E., et al.
(författare)
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Data availability, reusability, and analytic reproducibility : evaluating the impact of a mandatory open data policy at the journal Cognition
- 2018
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Ingår i: Royal Society Open Science. - : The Royal Society. - 2054-5703. ; 5:8
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Tidskriftsartikel (refereegranskat)abstract
- Access to data is a critical feature of an efficient, progressive and ultimately self-correcting scientific ecosystem. But the extent to which in-principle benefits of data sharing are realized in practice is unclear. Crucially, it is largely unknown whether published findings can be reproduced by repeating reported analyses upon shared data ('analytic reproducibility'). To investigate this, we conducted an observational evaluation of a mandatory open data policy introduced at the journal Cognition. Interrupted time-series analyses indicated a substantial post-policy increase in data available statements (104/417, 25% pre-policy to 136/ 174, 78% post-policy), although not all data appeared reusable (23/ 104, 22% pre-policy to 85/136, 62%, post-policy). For 35 of the articles determined to have reusable data, we attempted to reproduce 1324 target values. Ultimately, 64 values could not be reproduced within a 10% margin of error. For 22 articles all target values were reproduced, but 11 of these required author assistance. For 13 articles at least one value could not be reproduced despite author assistance. Importantly, there were no clear indications that original conclusions were seriously impacted. Mandatory open data policies can increase the frequency and quality of data sharing. However, suboptimal data curation, unclear analysis specification and reporting errors can impede analytic reproducibility, undermining the utility of data sharing and the credibility of scientific findings.
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| 9. |
- Rannikmaee, Kristiina, et al.
(författare)
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Common variation in COL4A1/COL4A2 is associated with sporadic cerebral small vessel disease
- 2015
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Ingår i: Neurology. - 1526-632X. ; 84:9, s. 918-926
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Tidskriftsartikel (refereegranskat)abstract
- Objectives:We hypothesized that common variants in the collagen genes COL4A1/COL4A2 are associated with sporadic forms of cerebral small vessel disease.Methods:We conducted meta-analyses of existing genotype data among individuals of European ancestry to determine associations of 1,070 common single nucleotide polymorphisms (SNPs) in the COL4A1/COL4A2 genomic region with the following: intracerebral hemorrhage and its subtypes (deep, lobar) (1,545 cases, 1,485 controls); ischemic stroke and its subtypes (cardioembolic, large vessel disease, lacunar) (12,389 cases, 62,004 controls); and white matter hyperintensities (2,733 individuals with ischemic stroke and 9,361 from population-based cohorts with brain MRI data). We calculated a statistical significance threshold that accounted for multiple testing and linkage disequilibrium between SNPs (p < 0.000084).Results:Three intronic SNPs in COL4A2 were significantly associated with deep intracerebral hemorrhage (lead SNP odds ratio [OR] 1.29, 95% confidence interval [CI] 1.14-1.46, p = 0.00003; r(2) > 0.9 between SNPs). Although SNPs associated with deep intracerebral hemorrhage did not reach our significance threshold for association with lacunar ischemic stroke (lead SNP OR 1.10, 95% CI 1.03-1.18, p = 0.0073), and with white matter hyperintensity volume in symptomatic ischemic stroke patients (lead SNP OR 1.07, 95% CI 1.01-1.13, p = 0.016), the direction of association was the same. There was no convincing evidence of association with white matter hyperintensities in population-based studies or with non-small vessel disease cerebrovascular phenotypes.Conclusions:Our results indicate an association between common variation in the COL4A2 gene and symptomatic small vessel disease, particularly deep intracerebral hemorrhage. These findings merit replication studies, including in ethnic groups of non-European ancestry.
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