Canary: an automated tool for the conversion of MaCH imputed dosage files to PLINK files.

BACKGROUND: Previous studies have demonstrated the value of re-analysing publicly available genetics data with recent analytical approaches. Publicly available datasets, such as the Women's Health Initiative (WHI) offered by the database of genotypes and phenotypes (dbGaP), provide a wealthy resource for researchers to perform multiple analyses, including Genome-Wide Association Studies. Often, the genetic information of individuals in these datasets are stored in imputed dosage files output by MaCH; mldose and mlinfo files. In order for researchers to perform GWAS studies with this data, they must first be converted to a file format compatible with their tool of choice e.g., PLINK. Currently, there is no published tool which easily converts the datasets provided in MACH dosage files into PLINK-ready files. RESULTS: Herein, we present Canary a singularity-based tool which converts MaCH dosage files into PLINK-compatible files with a single line of user input at the command line. Further, we provide a detailed tutorial on preparation of phenotype files. Moreover, Canary comes with preinstalled software often used during GWAS studies, to further increase the ease-of-use of HPC systems for researchers. CONCLUSIONS: Until now, conversion of imputed data in the form of MaCH mldose and mlinfo files needed to be completed manually. Canary uses singularity container technology to allow users to automatically convert these MaCH files into PLINK compatible files. Additionally, Canary provides researchers with a platform to conduct GWAS analysis more easily as it contains essential software needed for conducting GWAS studies, such as PLINK and Bioconductor. We hope that this tool will greatly increase the ease at which researchers can perform GWAS with imputed data, particularly on HPC environments.

IGFBP-1 in Cardiometabolic Pathophysiology-Insights From Loss-of-Function and Gain-of-Function Studies in Male Mice.

We have previously reported that overexpression of human insulin-like growth factor binding protein (IGFBP)-1 in mice leads to vascular insulin sensitization, increased nitric oxide bioavailability, reduced atherosclerosis, and enhanced vascular repair, and in the setting of obesity improves glucose tolerance. Human studies suggest that low levels of IGFBP-1 are permissive for the development of diabetes and cardiovascular disease. Here we seek to determine whether loss of IGFBP-1 plays a causal role in the predisposition to cardiometabolic disease. Metabolic phenotyping was performed in transgenic mice with homozygous knockout of IGFBP-1. This included glucose, insulin, and insulin-like growth factor I tolerance testing under normal diet and high-fat feeding conditions. Vascular phenotyping was then performed in the same mice using vasomotor aortic ring studies, flow cytometry, vascular wire injury, and angiogenesis assays. These were complemented with vascular phenotyping of IGFBP-1 overexpressing mice. Metabolic phenotype was similar in IGFBP-1 knockout and wild-type mice subjected to obesity. Deletion of IGFBP-1 inhibited endothelial regeneration following injury, suggesting that IGFBP-1 is required for effective vascular repair. Developmental angiogenesis was unaltered by deletion or overexpression of IGFBP-1. Recovery of perfusion following hind limb ischemia was unchanged in mice lacking or overexpressing IGFBP-1; however, overexpression of IGFBP-1 stimulated hindlimb perfusion and angiogenesis in insulin-resistant mice. These findings provide new insights into the role of IGFBP-1 in metabolic and vascular pathophysiology. Irrespective of whether loss of IGFBP-1 plays a causal role in the development of cardiometabolic disorders, increasing IGFBP-1 levels appears effective in promoting neovascularization in response to ischemia.