Trans-ancestry genome-wide association study identifies 12 genetic loci influencing blood pressure and implicates a role for DNA methylation

We carried out a trans-ancestry genome-wide association and replication study of blood pressure phenotypes among up to 320,251 individuals of East Asian, European and South Asian ancestry. We find genetic variants at 12 new loci to be associated with blood pressure (P = 3.9 × 10-11 to 5.0 × 10-21). The sentinel blood pressure SNPs are enriched for association with DNA methylation at multiple nearby CpG sites, suggesting that, at some of the loci identified, DNA methylation may lie on the regulatory pathway linking sequence variation to blood pressure. The sentinel SNPs at the 12 new loci point to genes involved in vascular smooth muscle (IGFBP3, KCNK3, PDE3A and PRDM6) and renal (ARHGAP24, OSR1, SLC22A7 and TBX2) function. The new and known genetic variants predict increased left ventricular mass, circulating levels of NT-proBNP, and cardiovascular and all-cause mortality (P = 0.04 to 8.6 × 10-6). Our results provide new evidence for the role of DNA methylation in blood pressure regulation

Congenital heart disease: cardiovascular MR imaging by using an intravascular blood pool contrast agent.

Item does not contain fulltextPURPOSE: To compare the image quality and diagnostic performance of a contrast agent-specific inversion-recovery (IR) steady-state free precession (SSFP) magnetic resonance (MR) imaging sequence performed by using an intravascular contrast agent (gadofosveset trisodium) with those of a commonly used T2-prepared SSFP sequence performed by using an extravascular (gadopentetate dimeglumine) and an intravascular (gadofosveset trisodium) contrast agent in patients with congenital heart disease (CHD). MATERIALS AND METHODS: The local ethics committee and the United Kingdom Medicines and Healthcare products Regulatory Agency approved this study. Patient informed consent was obtained. Twenty-three patients with CHD were examined by using a 1.5-T MR imaging unit and a 32-channel coil. Gadopentetate dimeglumine and gadofosveset trisodium were used in the same patient on consecutive days. Vessel wall sharpness, contrast-to-noise ratios (CNRs), image quality, and diagnostic performance achieved by using the IR SSFP sequence with gadofosveset trisodium were compared with those achieved by using the T2-prepared SSFP sequence with gadopentetate dimeglumine and gadofosveset trisodium and with those achieved at respective contrast material-enhanced MR angiographic examinations. The Wilcoxon rank sum test was used to compare categoric variables; t tests were used to compare continuous variables. RESULTS: Use of the IR SSFP sequence with gadofosveset trisodium significantly improved vessel wall sharpness, CNRs, and image quality (P < .05 for all) for all investigated intra- and extracardiac structures compared with the T2-prepared SSFP sequence with gadopentetate dimeglumine and gadofosveset trisodium and the respective contrast-enhanced MR angiographic examinations. With use of the IR SSFP sequence with gadofosveset trisodium, new, unsuspected diseases (five [22%] of 23) were diagnosed, while other diseases could be excluded (15 [65%] of 23). Information available from echocardiography (n = 23), conventional angiography (n = 4), and/or surgery (n = 1) confirmed all diagnoses. CONCLUSION: IR SSFP with gadofosveset trisodium improved image quality and diagnostic performance, allowing a more accurate and complete assessment of cardiovascular anatomy in patients with CHD compared with T2-prepared SSFP with gadopentetate dimeglumine and gadofosveset trisodium and respective contrast-enhanced MR angiographic examinations.1 september 201