Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Genome-wide association and Mendelian randomisation analysis provide insights into the pathogenesis of heart failure

Abstract: Heart failure (HF) is a leading cause of morbidity and mortality worldwide. A small proportion of HF cases are attributable to monogenic cardiomyopathies and existing genome-wide association studies (GWAS) have yielded only limited insights, leaving the observed heritability of HF largely unexplained. We report results from a GWAS meta-analysis of HF comprising 47,309 cases and 930,014 controls. Twelve independent variants at 11 genomic loci are associated with HF, all of which demonstrate one or more associations with coronary artery disease (CAD), atrial fibrillation, or reduced left ventricular function, suggesting shared genetic aetiology. Functional analysis of non-CAD-associated loci implicate genes involved in cardiac development (MYOZ1, SYNPO2L), protein homoeostasis (BAG3), and cellular senescence (CDKN1A). Mendelian randomisation analysis supports causal roles for several HF risk factors, and demonstrates CAD-independent effects for atrial fibrillation, body mass index, and hypertension. These findings extend our knowledge of the pathways underlying HF and may inform new therapeutic strategies

Highly Efficient Grating Coupler for Silicon Nitride Photonics with Large Fabrication Tolerance

We demonstrate low-loss fiber-to-chip coupling via a-Si grating couplers on top of SiN waveguides for C-band TE light. The suggested simple scheme is fabrication tolerant and offers a path towards coupling efficiencies above -1 dB

100 Gbit/s NRZ Data Modulation in Plasmonic Racetrack Modulators on the Silicon Photonic Platform

Low power broadband plasmonic silicon-photonic racetrack modulators are introduced. 100 Gbit/s NRZ-OOK and 100 Gbit/s 4-PAM direct detection is demonstrated. The devices feature a bandwidth of 50 GHz, operate with 1.3 V p and are of interest because of the low on-chip loss characteristics

Plasmonic Racetrack Modulator Transmitting 220 Gbit/s OOK and 408 Gbit/s 8PAM

OOK line rates of 220 Gbit/s and 408 Gbit/s 8PAM and transmission over 100 m are demonstrated with a resonant plasmonic racetrack modulator. The device requires low 0.6 Vp driver voltages, offers a bandwidth >110 GHz and on-chip losses of 1.0 dB

Resonant plasmonic micro-racetrack modulators with high bandwidth and high temperature tolerance

Resonant modulators encode electrical data onto wavelength-multiplexed optical carriers. Today, silicon microring modulators are perceived as promising to implement such links; however, they provide limited bandwidth and need thermal stabilization systems. Here we present plasmonic micro-racetrack modulators as a potential successor of silicon microrings: they are equally compact and compatible with complementary-metal–oxide–semiconductor-level driving voltages, but offer electro-optical bandwidths of 176 GHz, a 28 times improved stability against operating temperature changes and no self-heating effects. The temperature-resistant organic electro-optic material enables operation at 85 °C device temperature. We show intensity-modulated transmission of up to 408 Gbps at 12.3 femtojoules per bit with a single resonant modulator. Plasmonic micro-racetrack modulators offer a solution to encode high data rates (for example, the 1.6 Tbps envisioned by next-generation communications links) at a small footprint, with low power consumption and marginal, if no, temperature control.ISSN:1749-4885ISSN:1749-489

Enhanced Stability of Resonant Racetrack Plasmonic-Organic-Hybrid Modulators

A high-speed and compact plasmonic organic racetrack modulator is shown to be orders of magnitude more robust against operating condition changes compared to resonant modulators based on the plasma dispersion effect while maintaining thermal tunability. Stable operation at 80°C is shown with no degradation