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

Kimberlite, lamproite, ultramafic lamprophyre, carbonatite relationships on the Dharwar Craton, India; an example from the Khaderpet pipe, a diamondiferous ultramafic with associated carbonatite intrusion

Are kimberlites, lamproites, ultramafic lamprophyres and carbonatites genetically associated or not? There are strong opinions for and against any relationship. The 20 Ha Khaderpet pipe, discovered by Rio Tinto Exploration, is an unusual diamondiferous carbonatite-kimberlite clan rock (KCR) association in the Anumpalle Cluster of the Wajrakarur Kimberlite Field in the Dharwar Craton of Peninsular Indian. The Khaderpet pipe has a discrete sovite phase intrusive into KCR breccia, not noticed elsewhere in the Wajrakarur kimberlite field. Petrographically, the KCR is a clast-supported lithic breccia and crystal lithic tuff, with occasional pelletal lapilli. Clasts show a weak horizontal imbrication. The overall appearance of the tuffs and breccias is suggestive of terminal-blocked, vent accumulations that formed by under pressure, with spallation of country rock causing an abundance of granitoid debris. The sovite phase has up to 95% calcite, occasionally showing flow textured polycrystalline laths set in a minor saponite matrix. There are mineralogical gradations from an olivine-rich ultramafic to a calcite-dominant rock resembling pure carbonatite. Rare REE mineral phases in the carbonatite include allanite and other REE-rich unidentified mineral phases. Xenocrystic high pressure phases in both ultramafic and carbonatite include mantle-derived diamonds, lherzolitic -, eclogitic – and subcalcic-pyrope, Ti-poor andradite, chrome diopside, picrochromite and picroilmenite. Extensive metasomatism in the form of reddening of country rock feldspars by hematite, introduction of green chlorite, and saponitic alteration of breccia clasts and the ultramafic phase is common. The chemistry of the Khaderpet ultramafic component, suggests the KCR is transitional between kimberlite and ultramafic lamprophyres, like certain other pipes in the Wajrakarur Kimberlite Field, with strong enrichment in LREE, CaO and CO2. However, low MgO (~ 13%) and high CaO (~ 10%) values are more typical of ultramafic lamprophyres such as alnoite or aillikite. The significant carbonate content and the presence of accessory Ti-andradite would lead to the KCR being classified as an ultramafic lamprophyre under the IUGS classification. The Khaderpet carbonatite component shows extreme enrichment in REE approaching that of world-average carbonatite. Given the chemical and petrological characteristics of a carbonatite, along with the associated and widespread aureole of metasomatism, this phase is considered to be a late-stage fractionation product of the Khaderpet diamond-bearing ultramafic magma

Kimberlite-carbonatite relationships revisited: evidence from Khaderpet pipe, Andhra Pradesh, India

The 30 ha Khaderpet Pipe is a unique kimberlite – carbonatite association, one of 14 kimberlite pipes discovered by Rio Tinto Exploration (RTX) between 2001-2004 during its prospecting of the Wajrakarur Kimberlite Field (WKF)