The objective of this prospective study is to demonstrate the challenges faced by business organizations while adapting to the new digital landscape. The idea is to assist in breaking down the ...complex process of digital transformation and strengthen the management perspective in the area. The study argues how manufacturing exporting firms could develop a digital transformation strategy that includes a different aspect of the strategy tailored to the nature of the Indian exporting firms. Dealing with different aspects of digital transformation, the study discusses different perspectives such as core competencies, internal drivers of digital transformation (IDDT) and external drivers of digital transformation (EDDT), enablers of digital transformation (EDT), new capabilities required and strategic imperatives of digital transformation. Synthesizing digitalization through these lenses can help in developing and implementing a successful digital transformation strategy.
Over the last 10 years, there have been over 3300 genome-wide association studies (GWAS). Almost every GWAS study provides a Manhattan plot either as a main figure or in the supplement. Several ...software packages can generate a Manhattan plot, but they are all limited in the extent to which they can annotate gene-names, allele frequencies, and variants having high impact on gene function or provide any other added information or flexibility. Furthermore, in a conventional Manhattan plot, there is no way of distinguishing a locus identified due to a single variant with very significant p-value from a locus with multiple variants which appear to be in a haplotype block having very similar p-values.
Here we present a software tool written in R, which generates a transposed Manhattan plot along with additional features like variant consequence and minor allele frequency to annotate the plot and addresses these limitations. The software also gives flexibility on how and where the user wants to display the annotations. The software can be downloaded from CRAN repository and also from the GitHub project page.
We present a major step up to the existing conventional Manhattan plot generation tools. We hope this form of display along with the added annotations will bring more insight to the reader from this new Manhattan++ plot.
Abstract Background Although epidemiological studies have reported positive associations between circulating urate levels and cardiometabolic diseases, causality remains uncertain. Objectives Through ...a Mendelian randomization approach, we assessed whether serum urate levels are causally relevant in type 2 diabetes mellitus (T2DM), coronary heart disease (CHD), ischemic stroke, and heart failure (HF). Methods This study investigated 28 single nucleotide polymorphisms known to regulate serum urate levels in association with various vascular and nonvascular risk factors to assess pleiotropy. To limit genetic confounding, 14 single nucleotide polymorphisms exclusively associated with serum urate levels were used in a genetic risk score to assess associations with the following cardiometabolic diseases (cases/controls): T2DM (26,488/83,964), CHD (54,501/68,275), ischemic stroke (14,779/67,312), and HF (4,526/18,400). As a positive control, this study also investigated our genetic instrument in 3,151 gout cases and 68,350 controls. Results Serum urate levels, increased by 1 SD due to the genetic score, were not associated with T2DM, CHD, ischemic stroke, or HF. These results were in contrast with previous prospective studies that did observe increased risks of these 4 cardiometabolic diseases for an equivalent increase in circulating urate levels. However, a 1 SD increase in serum urate levels due to the genetic score was associated with increased risk of gout (odds ratio: 5.84; 95% confidence interval: 4.56 to 7.49), which was directionally consistent with previous observations. Conclusions Evidence from this study does not support a causal role of circulating serum urate levels in T2DM, CHD, ischemic stroke, or HF. Decreasing serum urate levels may not translate into risk reductions for cardiometabolic conditions.
Kaposi’s sarcoma (KS) is a cancer that often affects individuals with human immunodeficiency virus, acquired immunodeficiency syndrome (AIDS), those who have received an organ transplant, or others ...who are immunocompromised. KS is a vascular tumor that most often presents in cutaneous sites, including the lower extremities, oral mucosa, and genitalia. Literature regarding KS with ocular involvement is scarce. We present a rare case in which a patient diagnosed with AIDS-associated KS exhibited ocular and diffuse manifestations. The lesions of cutaneous KS are frequently mistaken for an alternative diagnoses; therefore, the clinician should have a high index of suspicion for this vascular tumor in AIDS patients.
CADM2 has been associated with a range of behavioural and metabolic traits, including physical activity, risk-taking, educational attainment, alcohol and cannabis use and obesity. Here, we set out to ...determine whether CADM2 contributes to mechanisms shared between mental and physical health disorders. We assessed genetic variants in the CADM2 locus for association with phenotypes in the UK Biobank, IMPROVE, PROCARDIS and SCARFSHEEP studies, before performing meta-analyses. A wide range of metabolic phenotypes were meta-analysed. Psychological phenotypes analysed in UK Biobank only were major depressive disorder, generalised anxiety disorder, bipolar disorder, neuroticism, mood instability and risk-taking behaviour. In UK Biobank, four, 88 and 172 genetic variants were significantly (p < 1 × 10
) associated with neuroticism, mood instability and risk-taking respectively. In meta-analyses of 4 cohorts, we identified 362, 63 and 11 genetic variants significantly (p < 1 × 10
) associated with BMI, SBP and CRP respectively. Genetic effects on BMI, CRP and risk-taking were all positively correlated, and were consistently inversely correlated with genetic effects on SBP, mood instability and neuroticism. Conditional analyses suggested an overlap in the signals for physical and psychological traits. Many significant variants had genotype-specific effects on CADM2 expression levels in adult brain and adipose tissues. CADM2 variants influence a wide range of both psychological and metabolic traits, suggesting common biological mechanisms across phenotypes via regulation of CADM2 expression levels in adipose tissue. Functional studies of CADM2 are required to fully understand mechanisms connecting mental and physical health conditions.
Progress in mapping loci associated with common complex diseases or quantitative inherited traits has been expedited by large-scale meta-analyses combining information across multiple studies, ...assembled through collaborative networks of researchers. Participating studies will usually have been independently designed and implemented in unique settings that are potential sources of phenotype, ancestry or other variability that could introduce between-study heterogeneity into a meta-analysis. Heterogeneity tests based on individual genetic variants (e.g. Q, I2) are not suited to identifying locus-specific from more systematic multi-locus or genome-wide patterns of heterogeneity. We have developed and evaluated an aggregate heterogeneity M statistic that combines between-study heterogeneity information across multiple genetic variants, to reveal systematic patterns of heterogeneity that elude conventional single variant analysis. Application to a GWAS meta-analysis of coronary disease with 48 contributing studies uncovered substantial systematic between-study heterogeneity, which could be partly explained by age-of-disease onset, family-history of disease and ancestry. Future meta-analyses of diseases and traits with multiple known genetic associations can use this approach to identify outlier studies and thereby optimize power to detect novel genetic associations.
Genome-wide association studies (GWAS) have identified over two hundred chromosomal loci that modulate risk of coronary artery disease (CAD). The genes affected by variants at these loci are largely ...unknown and an untapped resource to improve our understanding of CAD pathophysiology and identify potential therapeutic targets. Here, we prioritized 68 genes as the most likely causal genes at genome-wide significant loci identified by GWAS of CAD and examined their regulatory roles in 286 metabolic and vascular tissue gene-protein sub-networks ("modules"). The modules and genes within were scored for CAD druggability potential. The scoring enriched for targets of cardiometabolic drugs currently in clinical use and in-depth analysis of the top-scoring modules validated established and revealed novel target tissues, biological processes, and druggable targets. This study provides an unprecedented resource of tissue-defined gene-protein interactions directly affected by genetic variance in CAD risk loci.
Several genome-wide association studies have recently linked a group of single nucleotide polymorphisms in the 9p21 region with cardiovascular disease. The molecular mechanisms of this link are not ...fully understood. We investigated five different expression microarray datasets in order to determine if the genotype had effect on expression of any gene transcript in aorta, mammary artery, carotid plaque and lymphoblastoid cells.
After multiple testing correction, no genes were found to have relation to the rs2891168 risk genotype, either on a genome-wide scale or on a regional (8 MB) scale. The neighbouring ANRIL gene was found to have eight novel transcript variants not previously known from literature and these varied by tissue type. We therefore performed a detailed probe-level analysis and found small stretches of significant relation to genotype but no consistent associations. In all investigated tissues we found an inverse correlation between ANRIL and the MTAP gene and a positive correlation between ANRIL and CDKN2A and CDKN2B.
Investigation of relation of the risk genotype to gene expression is complicated by the transcript complexity of the locus. With our investigation of a range of relevant tissue we wish to underscore the need for careful attention to the complexity of the alternative splicing issues in the region and its implications to the design of future gene expression studies.
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