A simple method to localise pleiotropic susceptibility loci using univariate linkage analyses of correlated traits

Univariate linkage analysis is used routinely to localise genes for human complex traits. Often, many traits are analysed but the significance of linkage for each trait is not corrected for multiple trait testing, which increases the experiment-wise type-I error rate. In addition, univariate analyses do not realise the full power provided by multivariate data sets. Multivariate linkage is the ideal solution but it is computationally intensive, so genome-wide analysis and evaluation of empirical significance are often prohibitive. We describe two simple methods that efficiently alleviate these caveats by combining P-values from multiple univariate linkage analyses. The first method estimates empirical pointwise and genome-wide significance between one trait and one marker when multiple traits have been tested. It is as robust as an appropriate Bonferroni adjustment, with the advantage that no assumptions are required about the number of independent tests performed. The second method estimates the significance of linkage between multiple traits and one marker and, therefore, it can be used to localise regions that harbour pleiotropic quantitative trait loci (QTL). We show that this method has greater power than individual univariate analyses to detect a pleiotropic QTL across different situations. In addition, when traits are moderately correlated and the QTL influences all traits, it can outperform formal multivariate VC analysis. This approach is computationally feasible for any number of traits and was not affected by the residual correlation between traits. We illustrate the utility of our approach with a genome scan of three asthma traits measured in families with a twin proband.

Sub-epidemics explain localized high prevalence of reduced susceptibility to Rilpivirine in treatment-naive HIV-1-infected patients: subtype and geographic compartmentalization of baseline resistance mutations

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Testing a framework for the quality of process models: A case study

Process modeling can be regarded as the currently most popular form of conceptual modeling. Research evidence illustrates how process modeling is applied across the different information system life cycle phases for a range of different applications, such as configuration of Enterprise Systems, workflow management, or software development. However, a detailed discussion of critical factors of the quality of process models is still missing. This paper proposes a framework consisting of six quality factors, which is derived from a comprehensive literature review. It then presents in a case study, a utility provider, who had designed various business process models for the selection of an Enterprise System. The paper summarizes potential means of conducting a successful process modeling initiative and evaluates the described modeling approach within the Guidelines of Modeling (GoM) framework. An outlook shows the potential lessons learnt, and concludes with insights to the next phases of this study.

Entrepreneurial bricolage : towards systematic empirical testing

The behavioral theory of “entrepreneurial bricolage” attempts to understand what entrepreneurs do when faced with resource constraints. Most research about bricolage, defined as “making do by applying combinations of the resources at hand to new problems and opportunities” (Baker & Nelson 2005: 333), has been qualitative and inductive (Garud & Karnoe, 2003). Although this has created a small body of rich descriptions and interesting insights, little deductive theory has been developed and the relationship between bricolage and firm performance has not been systematically tested. In particular, prior research has suggested bricolage can have both beneficial and harmful effects. Ciborra’s (1996) study of Olivetti suggested that bricolage helped Olivetti to adapt, but simultaneously constrained firm effectiveness. Baker & Nelson (2005) suggested that bricolage may be harmful at very high levels, but more helpful if used judiciously. Other research suggests that firm innovativeness may play an important role in shaping the outcomes of bricolage (Anderson 2008). In this paper, we theorize and provide preliminary test of the bricolage-performance relationship and how it is affected by firm innovativeness.