We investigated type 2 diabetes (T2D) genetic susceptibility in a multi-ethnic meta-analysis of 228,499 cases and 1,178,783 controls in the Million Veteran Program (MVP) and other biobanks. We identified 558 autosomal and 10 X-chromosome T2D-associated variants, of which 286 autosomal and 7 X-chromosome variants were previously unreported. Ancestry-specific analyses identified 25 additional novel T2D-susceptibility variants. Transcriptome-wide association analysis detected 3,568 T2D-associations with T2D-colocalized genetically predicted gene expression of 804 genes in 52 tissues, of which 687 are novel. Fifty-four of these genes are known to interact with FDA-approved drugs and chemical compounds. T2D polygenic risk score was strongly associated with increased the risk of T2D-related retinopathy, and additionally showed evidence for association with chronic kidney disease (CKD), neuropathy, and peripheral artery disease (PAD). We investigated the genetic etiology of T2D-related vascular outcomes in the MVP and observed statistical SNP-T2D interactions at 13 variants, including 3 for coronary heart disease, 1 for PAD, 2 for stroke, 4 for retinopathy, 2 for CKD, and 1 for neuropathy. Our findings may identify potential novel therapeutic targets for T2D and genomic pathways that link T2D and its vascular outcomes.

Background Genetic, lifestyle, and environmental factors can lead to perturbations in circulating lipid levels and increase the risk of cardiovascular and metabolic diseases. However, how changes in individual lipid species contribute to disease risk is often unclear. Moreover, little is known about the role of lipids on cardiovascular disease in Pakistan, a population historically underrepresented in cardiovascular studies. Methods We characterised the genetic architecture of the human blood lipidome in 5662 hospital controls from the Pakistan Risk of Myocardial Infarction Study (PROMIS) and 13,814 healthy British blood donors from the INTERVAL study. We applied a candidate causal gene prioritisation tool to link the genetic variants associated with each lipid to the most likely causal genes, and Gaussian Graphical Modelling network analysis to identify and illustrate relationships between lipids and genetic loci. Results We identified 253 genetic associations with 181 lipids measured using direct infusion high-resolution mass spectrometry in PROMIS, and 502 genetic associations with 244 lipids in INTERVAL. Our analyses revealed new biological insights at genetic loci associated with cardiometabolic diseases, including novel lipid associations at the LPL, MBOAT7, LIPC, APOE-C1-C2-C4, SGPP1, and SPTLC3 loci. Conclusions Our findings, generated using a distinctive lipidomics platform in an understudied South Asian population, strengthen and expand the knowledge base of the genetic determinants of lipids and their association with cardiometabolic disease-related loci.

Background and Objective:Ventricular septal rupture (VSR) is one of the fatal complications of myocardial infarction (MI). Surgery provides the maximum survival benefit. Our objective was to investigate the risk factors of surgical mortality and to do the survival analysis in the past six years at our hospital.Methods:All the patients operated at CPE Institute of Cardiology Multan Pakistan, between 2009 and 2015 for repair of post MI VSR were analysed retrospectively for demographics, comorbidities, operative and post operative outcomes. The primary outcome was 30 days mortality. The follow up was done till April 2017 and the follow up data was obtained from hospital records and by telephoning the patients. SPSS was used for statistical analysis. P value < 0.05 was considered significant.Results:A total of 31 patients were operated for VSR repair with a mean age of 57.19±7.73 years. Eighteen patients also had a concomitant coronary artery bypass grafting (CABG). The operative mortality in this series was 25.8% Univariate analysis showed that pre-operative ejection fraction (E.F) (p value 0.010) and cardiogenic shock (p value 0.031) were a significant risk factors for operative mortality while on logistic regression analysis only the cardiogenic shock was found to be an independent risk factor for operative mortality with the odds ratio of 2.17. Low ejection fraction only acted as a confounding variable. The mean survival at six years was 34 months with a survival rate of 28.6%. The additional CABG did not confer any survival benefit.Conclusion:The patients in cardiogenic shock pre-operatively have a high operative mortality. Low ejection fraction (E.F) acts as a confounding factor. Concomitant CABG does not confer any survival benefit.

We report a case of young male patient who developed left internal mammary artery to pulmonary artery fistula 9 years following the coronary artery bypass grafting operation. The clinical signs and symptoms were very subtle including recurrence of angina and heart murmur. Surgical division of the fistula and re-grafting of blocked coronary arteries resulted in satisfactory long term outcome.