ResearchPad - replication-studies https://www.researchpad.co Default RSS Feed en-us © 2020 Newgen KnowledgeWorks <![CDATA[Warm, lively, rough? Assessing agreement on aesthetic effects of artworks]]> https://www.researchpad.co/article/elastic_article_13856 The idea that simple visual elements such as colors and lines have specific, universal associations—for example red being warm—appears rather intuitive. Such associations have formed a basis for the description of artworks since the 18th century and are still fundamental to discourses on art today. Art historians might describe a painting where red is dominant as “warm,” “aggressive,” or “lively,” with the tacit assumption that beholders would universally associate the works’ certain key forms with specific qualities, or “aesthetic effects”. However, is this actually the case? Do we actually share similar responses to the same line or color? In this paper, we tested whether and to what extent this assumption of universality (sharing of perceived qualities) is justified. We employed—for the first time—abstract artworks as well as single elements (lines and colors) extracted from these artworks in an experiment in which participants rated the stimuli on 14 “aesthetic effect” scales derived from art literature and empirical aesthetics. To test the validity of the assumption of universality, we examined on which of the dimensions there was agreement, and investigated the influence of art expertise, comparing art historians with lay people. In one study and its replication, we found significantly lower agreement than expected. For the whole artworks, participants agreed on the effects of warm-cold, heavy-light, and happy-sad, but not on 11 other dimensions. Further, we found that the image type (artwork or its constituting elements) was a major factor influencing agreement; people agreed more on the whole artwork than on single elements. Art expertise did not play a significant role and agreement was especially low on dimensions usually of interest in empirical aesthetics (e.g., like-dislike). Our results challenge the practice of interpreting artworks based on their aesthetic effects, as these effects may not be as universal as previously thought.

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<![CDATA[Partition dependence in financial aid distribution to income categories]]> https://www.researchpad.co/article/N0611b39b-d559-4542-a5d9-a69c54a62df4

When allocating resources, people often diversify across categories even when those categories are arbitrary, such that allocations differ when identical sets of options are partitioned differently (“partition dependence”). The first goal of the present work (Experiment 1) was to replicate an experiment by Fox and colleagues in which graduate students exhibited partition dependence when asked how university financial aid should be allocated across arbitrarily partitioned income brackets. Our sample consisted of community members at a liberal arts college where financial aid practices have been recent topics of debate. Because stronger intrinsic preferences can reduce partition dependence, these participants might display little partition dependence with financial aid allocations. Alternatively, a demonstration of strong partition dependence in this population would emphasize the robustness of the effect. The second goal was to extend a “high transparency” modification to the present task context (Experiment 2) in which participants were shown both possible income partitions and randomly assigned themselves to one, to determine whether partition dependence in this paradigm would be reduced by revealing the study design (and the arbitrariness of income categories). Participants demonstrated clear partition dependence in both experiments. Results demonstrate the robustness of partition dependence in this context.

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<![CDATA[Treatment of HIV among tuberculosis patients: A replication study of timing of antiretroviral therapy for HIV-1-associated tuberculosis]]> https://www.researchpad.co/article/5c5df36fd5eed0c4845812c9

Co-diagnosis of HIV and tuberculosis presents a treatment dilemma. Starting both treatments at the same time can cause a flood of immune response called immune reconstitution inflammatory syndrome (IRIS) which can be lethal. But, how long to delay HIV treatment is less understood. In 2011, based on the conclusions of three separate studies, WHO recommended starting HIV treatment earlier for those with later HIV disease progression. This paper conducts a replication study of one of the three studies, by Havlir and colleagues. Using their publicly available data, we were able to replicate most of the results presented in the original paper. In our measurement and estimation analyses we use different estimation techniques to assess the robustness of the results. We find that adjusting for loss to follow-up does not affect the main results of the paper. However, an ANCOVA estimation and an instrumental variable model weaken the main result of the paper of better outcomes with early HIV treatment only for those who are sicker, reducing significance from the 5% to the 10% level. A change-point analysis also detects no changes in effect by timing of HIV treatment initiation or different thresholds of CD4 count for the primary outcome. This result suggests that the choice of start time for HIV treatment initiation should be based on other factors including potential drug interactions, overlapping side effects, a high pill burden and severity of illness rather than CD4 threshold and preset timeframes. While we caution against overgeneralizing, the result of this replication is aligned with more recent studies that show no evidence that early initiation of HIV treatment reduces mortality for any patients.

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<![CDATA[Cash transfers and HIV/HSV-2 prevalence: A replication of a cluster randomized trial in Malawi]]> https://www.researchpad.co/article/5c5ca315d5eed0c48441f0e5

Introduction

In this paper we perform a replication analysis of “Effect of a cash transfer programme for schooling on prevalence of HIV and herpes simplex type 2 in Malawi: a cluster randomised trial” by Sarah Baird and others published in “The Lancet” in 2012. The original study was a two-year cluster randomized intervention trial of never married girls aged 13–22 in Malawi. Enumeration areas were randomized to either an intervention involving cash transfer (conditional or unconditional of school enrollment) or control. The study included 1708 Malawian girls, who were enrolled at baseline and had biological testing for HIV and herpes simplex virus type 2 (HSV-2) at 18 months. The original findings showed that in the cohort of girls enrolled in school at baseline, the intervention had an effect on school enrollment, sexual outcomes, and HIV and HSV-2 prevalence. However, in the baseline school dropout cohort, the original study showed no intervention effect on HIV and HSV-2 prevalence.

Methods

We performed a replication of the study to investigate the consistency and robustness of key results reported. A pre-specified replication plan was approved and published online. Cleaned data was obtained from the original authors. A pure replication was conducted by reading the methods section and reproducing the results and tables found in the original paper. Robustness of the results were examined with alternative analysis methods in a measurement and estimation analysis (MEA) approach. A theory of change analysis was performed testing a causal pathway, the effect of intervention on HIV awareness, and whether the intervention effect depended on the wealth of the individual.

Results

The pure replication found that other than a few minor discrepancies, the original study was well replicated. However, the randomization and sampling weights could not be verified due to the lack of access to raw data and a detailed sample selection plan. Therefore, we are unable to determine how sampling influenced the results, which could be highly dependent on the sample. In MEA it was found that the intervention effect on HIV prevalence in the baseline schoolgirls cohort was somewhat sensitive to model choice, with a non-significant intervention effect for HIV depending on the statistical model used. The intervention effect on HSV-2 prevalence was more robust in terms of statistical significance, however, the odds ratios and confidence intervals differed from the original result by more than 10%. A theory of change analysis showed no effect of intervention on HIV awareness. In a causal pathway analysis, several variables were partial mediators, or potential mediators, indicating that the intervention could be working through its effect on school enrollment or selected sexual behaviors.

Conclusions

The effect of intervention on HIV prevalence in the baseline schoolgirls was sensitive to the model choice; however, HSV-2 prevalence results were confirmed. We recommend that the results from the original published analysis indicating the impact of cash transfers on HIV prevalence be treated with caution.

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<![CDATA[Testing the effect of cooperative/competitive priming on the Prisoner’s Dilemma. A replication study]]> https://www.researchpad.co/article/5c254575d5eed0c48442c7b8

The replicability crisis in psychology demands direct replications to test the reliability of relevant phenomena. Prime-to-behavior effects have been an area under intense scrutiny given its surprising results. However, intuitive unsurprising effects have been mostly neglected, while they may lack robustness as well. In the present study, we focused on an intuitive prime-to-behavior effect in which Kay and Ross (2003) used a 2x2 design to test cooperation/competition priming crossed with an explicit/non-explicit construal of a Prisoner’s Dilemma (PD). They found a stronger assimilation effect of priming when the situational construal anteceded the decision, but we could not reproduce their findings in the present close replication, despite counting on higher power. Even with limitations due to the unavailability of original materials, this replication presents evidence that questions the existence of the original finding, and highlights the need for further replications to get a deeper understanding of the hypothesized effect. The complete project is available at: https://osf.io/dhfns/.

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<![CDATA[Reproducible research practices, transparency, and open access data in the biomedical literature, 2015–2017]]> https://www.researchpad.co/article/5bfdb36ad5eed0c4845c9513

Currently, there is a growing interest in ensuring the transparency and reproducibility of the published scientific literature. According to a previous evaluation of 441 biomedical journals articles published in 2000–2014, the biomedical literature largely lacked transparency in important dimensions. Here, we surveyed a random sample of 149 biomedical articles published between 2015 and 2017 and determined the proportion reporting sources of public and/or private funding and conflicts of interests, sharing protocols and raw data, and undergoing rigorous independent replication and reproducibility checks. We also investigated what can be learned about reproducibility and transparency indicators from open access data provided on PubMed. The majority of the 149 studies disclosed some information regarding funding (103, 69.1% [95% confidence interval, 61.0% to 76.3%]) or conflicts of interest (97, 65.1% [56.8% to 72.6%]). Among the 104 articles with empirical data in which protocols or data sharing would be pertinent, 19 (18.3% [11.6% to 27.3%]) discussed publicly available data; only one (1.0% [0.1% to 6.0%]) included a link to a full study protocol. Among the 97 articles in which replication in studies with different data would be pertinent, there were five replication efforts (5.2% [1.9% to 12.2%]). Although clinical trial identification numbers and funding details were often provided on PubMed, only two of the articles without a full text article in PubMed Central that discussed publicly available data at the full text level also contained information related to data sharing on PubMed; none had a conflicts of interest statement on PubMed. Our evaluation suggests that although there have been improvements over the last few years in certain key indicators of reproducibility and transparency, opportunities exist to improve reproducible research practices across the biomedical literature and to make features related to reproducibility more readily visible in PubMed.

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<![CDATA[Significant association of RNF213 p.R4810K, a moyamoya susceptibility variant, with coronary artery disease]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc7db

Background

The genetic architecture of coronary artery disease has not been fully elucidated, especially in Asian countries. Moyamoya disease is a progressive cerebrovascular disease that is reported to be complicated by coronary artery disease. Because most Japanese patients with moyamoya disease carry the p.R4810K variant of the ring finger 213 gene (RNF213), this may also be a risk factor for coronary artery disease; however, this possibility has never been tested.

Methods and results

We genotyped the RNF213 p.R4810K variant in 956 coronary artery disease patients and 716 controls and tested the association between p.R4810K and coronary artery disease. We also validated the association in an independent population of 311 coronary artery disease patients and 494 controls. In the replication study, the p.R4810K genotypes were imputed from genome-wide genotyping data based on the 1000 Genomes Project. We used multivariate logistic regression analyses to adjust for well-known risk factors such as dyslipidemia and smoking habits. In the primary study population, the frequency of the minor variant allele was significantly higher in patients with coronary artery disease than in controls (2.04% vs. 0.98%), with an odds ratio of 2.11 (p = 0.017). Under a dominant model, after adjustment for risk factors, the association remained significant, with an odds ratio of 2.90 (95% confidence interval: 1.37–6.61; p = 0.005). In the replication study, the association was significant after adjustment for age and sex (odds ratio = 4.99; 95% confidence interval: 1.16–21.53; p = 0.031), although it did not reach statistical significance when further adjusted for risk factors (odds ratio = 3.82; 95% confidence interval: 0.87–16.77; p = 0.076).

Conclusions

The RNF213 p.R4810K variant appears to be significantly associated with coronary artery disease in the Japanese population.

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<![CDATA[A Bayesian Perspective on the Reproducibility Project: Psychology]]> https://www.researchpad.co/article/5989da55ab0ee8fa60b8eba5

We revisit the results of the recent Reproducibility Project: Psychology by the Open Science Collaboration. We compute Bayes factors—a quantity that can be used to express comparative evidence for an hypothesis but also for the null hypothesis—for a large subset (N = 72) of the original papers and their corresponding replication attempts. In our computation, we take into account the likely scenario that publication bias had distorted the originally published results. Overall, 75% of studies gave qualitatively similar results in terms of the amount of evidence provided. However, the evidence was often weak (i.e., Bayes factor < 10). The majority of the studies (64%) did not provide strong evidence for either the null or the alternative hypothesis in either the original or the replication, and no replication attempts provided strong evidence in favor of the null. In all cases where the original paper provided strong evidence but the replication did not (15%), the sample size in the replication was smaller than the original. Where the replication provided strong evidence but the original did not (10%), the replication sample size was larger. We conclude that the apparent failure of the Reproducibility Project to replicate many target effects can be adequately explained by overestimation of effect sizes (or overestimation of evidence against the null hypothesis) due to small sample sizes and publication bias in the psychological literature. We further conclude that traditional sample sizes are insufficient and that a more widespread adoption of Bayesian methods is desirable.

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<![CDATA[Genome-Wide Pharmacogenomic Study on Methadone Maintenance Treatment Identifies SNP rs17180299 and Multiple Haplotypes on CYP2B6, SPON1, and GSG1L Associated with Plasma Concentrations of Methadone R- and S-enantiomers in Heroin-Dependent Patients]]> https://www.researchpad.co/article/5989db40ab0ee8fa60bd6944

Methadone maintenance treatment (MMT) is commonly used for controlling opioid dependence, preventing withdrawal symptoms, and improving the quality of life of heroin-dependent patients. A steady-state plasma concentration of methadone enantiomers, a measure of methadone metabolism, is an index of treatment response and efficacy of MMT. Although the methadone metabolism pathway has been partially revealed, no genome-wide pharmacogenomic study has been performed to identify genetic determinants and characterize genetic mechanisms for the plasma concentrations of methadone R- and S-enantiomers. This study was the first genome-wide pharmacogenomic study to identify genes associated with the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites in a methadone maintenance cohort. After data quality control was ensured, a dataset of 344 heroin-dependent patients in the Han Chinese population of Taiwan who underwent MMT was analyzed. Genome-wide single-locus and haplotype-based association tests were performed to analyze four quantitative traits: the plasma concentrations of methadone R- and S-enantiomers and their respective metabolites. A significant single nucleotide polymorphism (SNP), rs17180299 (raw p = 2.24 × 10−8), was identified, accounting for 9.541% of the variation in the plasma concentration of the methadone R-enantiomer. In addition, 17 haplotypes were identified on SPON1, GSG1L, and CYP450 genes associated with the plasma concentration of methadone S-enantiomer. These haplotypes accounted for approximately one-fourth of the variation of the overall S-methadone plasma concentration. The association between the S-methadone plasma concentration and CYP2B6, SPON1, and GSG1L were replicated in another independent study. A gene expression experiment revealed that CYP2B6, SPON1, and GSG1L can be activated concomitantly through a constitutive androstane receptor (CAR) activation pathway. In conclusion, this study revealed new genes associated with the plasma concentration of methadone, providing insight into the genetic foundation of methadone metabolism. The results can be applied to predict treatment responses and methadone-related deaths for individualized MMTs.

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<![CDATA[A Puzzle Unsolved: Failure to Observe Different Effects of God and Religion Primes on Intergroup Attitudes]]> https://www.researchpad.co/article/5989db3dab0ee8fa60bd55db

Religious priming has been found to have both positive and negative consequences, and recent research suggests that the activation of God-related and community-related religious cognitions may cause outgroup prosociality and outgroup derogation respectively. The present research sought to examine whether reminders of God and religion have different effects on attitudes towards ingroup and outgroup members. Over two studies, little evidence was found for different effects of these two types of religious primes. In study 1, individuals primed with the words “religion”, “God” and a neutral control word evaluated both ingroup and outgroup members similarly, although a marginal tendency towards more negative evaluations of outgroup members by females exposed to religion primes was observed. In study 2, no significant differences in attitudes towards an outgroup member were observed between the God, religion, and neutral priming conditions. Furthermore, the gender effect observed in study 1 did not replicate in this second study. Possible explanations for these null effects are discussed.

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<![CDATA[The Idea Is Good, but…: Failure to Replicate Associations of Oxytocinergic Polymorphisms with Face-Inversion in the N170]]> https://www.researchpad.co/article/5989db44ab0ee8fa60bd7cec

Background

In event-related potentials, the N170 manifests itself especially in reaction to faces. In the healthy population, face-inversion leads to stronger negative amplitudes and prolonged latencies of the N170, effects not being present in patients with autism-spectrum-disorder (ASD). ASD has frequently been associated with differences in oxytocinergic neurotransmission. This ERP-study aimed to investigate the face-inversion effect in association with oxytocinergic candidate genes. It was expected that risk-allele-carriers of the oxytocin-receptor-gene-polymorphism (rs53576) and of CD38 (rs379863) responded similar to upright and inverted faces as persons with ASD. Additionally, reactions to different facial emotional expressions were studied. As there have been difficulties with replications of those molecular genetic association studies, we aimed to replicate our findings in a second study.

Method

Seventy-two male subjects in the first-, and seventy-eight young male subjects in the replication-study conducted a face-inversion-paradigm, while recording EEG. DNA was extracted from buccal cells.

Results

Results revealed stronger N170-amplitudes and longer latencies in reaction to inverted faces in comparison to upright ones. Furthermore, effects of emotion on N170 were evident. Those effects were present in the first and in the second study. Whereas we found molecular-genetic associations of oxytocinergic polymorphisms with the N170 in the first study, we failed to do so in the replication sample.

Conclusion

Results indicate that a deeper theoretical understanding of this research-field is needed, in order to generate possible explanations for these findings. Results, furthermore, support the hypotheses that success of reproducibility is correlated with strength of lower original p-values and larger effect sizes in the original study.

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<![CDATA[Wolf Lethal Control and Livestock Depredations: Counter-Evidence from Respecified Models]]> https://www.researchpad.co/article/5989da3cab0ee8fa60b884be

We replicated the study conducted by Wielgus and Peebles (2014) on the effect of wolf mortality on livestock depredations in Montana, Wyoming and Idaho states in the US. Their best models were found to be misspecified due to the omission of the time index and incorrect functional form. When we respecified the models, this replication failed to confirm the magnitude, direction and often the very existence of the original results. Wielgus and Peebles (2014) reported that the increase in the number of wolves culled the previous year would increase the expected number of livestock killed this year by 4 to 6%. But our results showed that the culling of one wolf the previous year would decrease the expected number of cattle killed this year by 1.9%, and the expected number of sheep killed by 3.4%. However, for every wolf killed there is a corresponding 2.2% increase in the expected number of sheep killed in the same year. The increase in sheep depredation appears to be a short term phenomenon.

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<![CDATA[Genomewide Association Study of African Children Identifies Association of SCHIP1 and PDE8A with Facial Size and Shape]]> https://www.researchpad.co/article/5989da4aab0ee8fa60b8cb7a

The human face is a complex assemblage of highly variable yet clearly heritable anatomic structures that together make each of us unique, distinguishable, and recognizable. Relatively little is known about the genetic underpinnings of normal human facial variation. To address this, we carried out a large genomewide association study and two independent replication studies of Bantu African children and adolescents from Mwanza, Tanzania, a region that is both genetically and environmentally relatively homogeneous. We tested for genetic association of facial shape and size phenotypes derived from 3D imaging and automated landmarking of standard facial morphometric points. SNPs within genes SCHIP1 and PDE8A were associated with measures of facial size in both the GWAS and replication cohorts and passed a stringent genomewide significance threshold adjusted for multiple testing of 34 correlated traits. For both SCHIP1 and PDE8A, we demonstrated clear expression in the developing mouse face by both whole-mount in situ hybridization and RNA-seq, supporting their involvement in facial morphogenesis. Ten additional loci demonstrated suggestive association with various measures of facial shape. Our findings, which differ from those in previous studies of European-derived whites, augment understanding of the genetic basis of normal facial development, and provide insights relevant to both human disease and forensics.

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<![CDATA[When those who know do share: Group goals facilitate information sharing, but social power does not undermine it]]> https://www.researchpad.co/article/5c900d08d5eed0c48407de75

Good team decisions require that team members share information with each other. Yet, members often tend to selfishly withhold important information. Does this tendency depend on their power within the team? Power-holders frequently act more selfishly (than the powerless)—accordingly, they might be tempted to withhold information. We predicted that given a task goal to ‘solve a task’, power-holders would selfishly share less information than the powerless. However, a group goal to ‘solve the task together’ would compensate for this selfishness, heightening particularly power-holders’ information sharing. In parallel, an individual goal to ‘solve the task alone’ may heighten selfishness and lower information sharing (even) among the powerless. We report five experiments (N = 1305), comprising all studies conducted in their original order. Analyses yielded weak to no evidence for these predictions; the findings rather supported the beneficial role of a group goal to ensure information sharing for both the powerful and the powerless.

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<![CDATA[No Evidence for a Saccadic Range Effect for Visually Guided and Memory-Guided Saccades in Simple Saccade-Targeting Tasks]]> https://www.researchpad.co/article/5989dab7ab0ee8fa60bad40f

Saccades to single targets in peripheral vision are typically characterized by an undershoot bias. Putting this bias to a test, Kapoula [1] used a paradigm in which observers were presented with two different sets of target eccentricities that partially overlapped each other. Her data were suggestive of a saccadic range effect (SRE): There was a tendency for saccades to overshoot close targets and undershoot far targets in a block, suggesting that there was a response bias towards the center of eccentricities in a given block. Our Experiment 1 was a close replication of the original study by Kapoula [1]. In addition, we tested whether the SRE is sensitive to top-down requirements associated with the task, and we also varied the target presentation duration. In Experiments 1 and 2, we expected to replicate the SRE for a visual discrimination task. The simple visual saccade-targeting task in Experiment 3, entailing minimal top-down influence, was expected to elicit a weaker SRE. Voluntary saccades to remembered target locations in Experiment 3 were expected to elicit the strongest SRE. Contrary to these predictions, we did not observe a SRE in any of the tasks. Our findings complement the results reported by Gillen et al. [2] who failed to find the effect in a saccade-targeting task with a very brief target presentation. Together, these results suggest that unlike arm movements, saccadic eye movements are not biased towards making saccades of a constant, optimal amplitude for the task.

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<![CDATA[Prediction Interval: What to Expect When You’re Expecting … A Replication]]> https://www.researchpad.co/article/5989da0cab0ee8fa60b77f8b

A challenge when interpreting replications is determining whether the results of a replication “successfully” replicate the original study. Looking for consistency between two studies is challenging because individual studies are susceptible to many sources of error that can cause study results to deviate from each other and the population effect in unpredictable directions and magnitudes. In the current paper, we derive methods to compute a prediction interval, a range of results that can be expected in a replication due to chance (i.e., sampling error), for means and commonly used indexes of effect size: correlations and d-values. The prediction interval is calculable based on objective study characteristics (i.e., effect size of the original study and sample sizes of the original study and planned replication) even when sample sizes across studies are unequal. The prediction interval provides an a priori method for assessing if the difference between an original and replication result is consistent with what can be expected due to sample error alone. We provide open-source software tools that allow researchers, reviewers, replicators, and editors to easily calculate prediction intervals.

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<![CDATA[Next-Generation Sequencing and In Vitro Expression Study of ADAMTS13 Single Nucleotide Variants in Deep Vein Thrombosis]]> https://www.researchpad.co/article/5989da39ab0ee8fa60b871a5

Background

Deep vein thrombosis (DVT) genetic predisposition is partially known.

Objectives

This study aimed at assessing the functional impact of nine ADAMTS13 single nucleotide variants (SNVs) previously reported to be associated as a group with DVT in a burden test and the individual association of selected variants with DVT risk in two replication studies.

Methods

Wild-type and mutant recombinant ADAMTS13 were transiently expressed in HEK293 cells. Antigen and activity of recombinant ADAMTS13 were measured by ELISA and FRETS-VWF73 assays, respectively. The replication studies were performed in an Italian case-control study (Milan study; 298/298 patients/controls) using a next-generation sequencing approach and in a Dutch case-control study (MEGA study; 4306/4887 patients/controls) by TaqMan assays.

Results

In vitro results showed reduced ADAMTS13 activity for three SNVs (p.Val154Ile [15%; 95% confidence interval [CI] 14–16], p.Asp187His [19%; 95%[CI] 17–21], p.Arg421Cys [24%; 95%[CI] 22–26]) similar to reduced plasma ADAMTS13 levels of patients carriers for these SNVs. Therefore these three SNVs were interrogated for risk association. The first replication study identified 3 heterozygous carriers (2 cases, 1 control) of p.Arg421Cys (odds ratio [OR] 2, 95%[CI] 0.18–22.25). The second replication study identified 2 heterozygous carriers (1 case, 1 control) of p.Asp187His ([OR] 1.14, 95%[CI] 0.07–18.15) and 10 heterozygous carriers (4 cases, 6 controls) of p.Arg421Cys ([OR] 0.76, 95%[CI] 0.21–2.68).

Conclusions

Three SNVs (p.Val154Ile, p.Asp187His and p.Arg421Cys) showed reduced ex vivo and in vitro ADAMTS13 levels. However, the low frequency of these variants makes it difficult to confirm their association with DVT.

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<![CDATA[No Reliable Association between Runs of Homozygosity and Schizophrenia in a Well-Powered Replication Study]]> https://www.researchpad.co/article/5989db0aab0ee8fa60bc9e33

It is well known that inbreeding increases the risk of recessive monogenic diseases, but it is less certain whether it contributes to the etiology of complex diseases such as schizophrenia. One way to estimate the effects of inbreeding is to examine the association between disease diagnosis and genome-wide autozygosity estimated using runs of homozygosity (ROH) in genome-wide single nucleotide polymorphism arrays. Using data for schizophrenia from the Psychiatric Genomics Consortium (n = 21,868), Keller et al. (2012) estimated that the odds of developing schizophrenia increased by approximately 17% for every additional percent of the genome that is autozygous (β = 16.1, CI(β) = [6.93, 25.7], Z = 3.44, p = 0.0006). Here we describe replication results from 22 independent schizophrenia case-control datasets from the Psychiatric Genomics Consortium (n = 39,830). Using the same ROH calling thresholds and procedures as Keller et al. (2012), we were unable to replicate the significant association between ROH burden and schizophrenia in the independent PGC phase II data, although the effect was in the predicted direction, and the combined (original + replication) dataset yielded an attenuated but significant relationship between Froh and schizophrenia (β = 4.86,CI(β) = [0.90,8.83],Z = 2.40,p = 0.02). Since Keller et al. (2012), several studies reported inconsistent association of ROH burden with complex traits, particularly in case-control data. These conflicting results might suggest that the effects of autozygosity are confounded by various factors, such as socioeconomic status, education, urbanicity, and religiosity, which may be associated with both real inbreeding and the outcome measures of interest.

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<![CDATA[Adult onset asthma and interaction between genes and active tobacco smoking: The GABRIEL consortium]]> https://www.researchpad.co/article/5989db52ab0ee8fa60bdc7dd

Background

Genome-wide association studies have identified novel genetic associations for asthma, but without taking into account the role of active tobacco smoking. This study aimed to identify novel genes that interact with ever active tobacco smoking in adult onset asthma.

Methods

We performed a genome-wide interaction analysis in six studies participating in the GABRIEL consortium following two meta-analyses approaches based on 1) the overall interaction effect and 2) the genetic effect in subjects with and without smoking exposure. We performed a discovery meta-analysis including 4,057 subjects of European descent and replicated our findings in an independent cohort (LifeLines Cohort Study), including 12,475 subjects.

Results

First approach: 50 SNPs were selected based on an overall interaction effect at p<10−4. The most pronounced interaction effect was observed for rs9969775 on chromosome 9 (discovery meta-analysis: ORint = 0.50, p = 7.63*10−5, replication: ORint = 0.65, p = 0.02). Second approach: 35 SNPs were selected based on the overall genetic effect in exposed subjects (p <10−4). The most pronounced genetic effect was observed for rs5011804 on chromosome 12 (discovery meta-analysis ORint = 1.50, p = 1.21*10−4; replication: ORint = 1.40, p = 0.03).

Conclusions

Using two genome-wide interaction approaches, we identified novel polymorphisms in non-annotated intergenic regions on chromosomes 9 and 12, that showed suggestive evidence for interaction with active tobacco smoking in the onset of adult asthma.

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<![CDATA[Scientists’ Reputations Are Based on Getting It Right, Not Being Right]]> https://www.researchpad.co/article/5989dad0ab0ee8fa60bb5ecf

Replication is vital for increasing precision and accuracy of scientific claims. However, when replications “succeed” or “fail,” they could have reputational consequences for the claim’s originators. Surveys of United States adults (N = 4,786), undergraduates (N = 428), and researchers (N = 313) showed that reputational assessments of scientists were based more on how they pursue knowledge and respond to replication evidence, not whether the initial results were true. When comparing one scientist that produced boring but certain results with another that produced exciting but uncertain results, opinion favored the former despite researchers’ belief in more rewards for the latter. Considering idealized views of scientific practices offers an opportunity to address incentives to reward both innovation and verification.

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