Large-scale analyses of common and rare variants identify 12 new loci associated with atrial fibrillation

Atrial fibrillation affects more than 33 million people worldwide and increases the risk of stroke, heart failure, and death. Fourteen genetic loci have been associated with atrial fibrillation in European and Asian ancestry groups. To further define the genetic basis of atrial fibrillation, we performed large-scale, trans-ancestry meta-analyses of common and rare variant association studies. The genome-wide association studies (GWAS) included 17,931 individuals with atrial fibrillation and 115,142 referents; the exome-wide association studies (ExWAS) and rare variant association studies (RVAS) involved 22,346 cases and 132,086 referents. We identified 12 new genetic loci that exceeded genome-wide significance, implicating genes involved in cardiac electrical and structural remodeling. Our results nearly double the number of known genetic loci for atrial fibrillation, provide insights into the molecular basis of atrial fibrillation, and may facilitate the identification of new potential targets for drug discovery

Multi-ethnic genome-wide association study for atrial fibrillation

Atrial fibrillation (AF) affects more than 33 million individuals worldwide and has a complex heritability. We conducted the largest meta-analysis of genome-wide association studies (GWAS) for AF to date, consisting of more than half a million individuals, including 65,446 with AF. In total, we identified 97 loci significantly associated with AF, including 67 that were novel in a combined-ancestry analysis, and 3 that were novel in a European-specific analysis. We sought to identify AF-associated genes at the GWAS loci by performing RNA-sequencing and expression quantitative trait locus analyses in 101 left atrial samples, the most relevant tissue for AF. We also performed transcriptome-wide analyses that identified 57 AF-associated genes, 42 of which overlap with GWAS loci. The identified loci implicate genes enriched within cardiac developmental, electrophysiological, contractile and structural pathways. These results extend our understanding of the biological pathways underlying AF and may facilitate the development of therapeutics for AF

Bedrock geology of DFDP-2B, central Alpine Fault, New Zealand

<p>During the second phase of the Alpine Fault, Deep Fault Drilling Project (DFDP) in the Whataroa River, South Westland, New Zealand, bedrock was encountered in the DFDP-2B borehole from 238.5–893.2 m Measured Depth (MD). Continuous sampling and meso- to microscale characterisation of whole rock cuttings established that, in sequence, the borehole sampled amphibolite facies, Torlesse Composite Terrane-derived schists, protomylonites and mylonites, terminating 200–400 m above an Alpine Fault Principal Slip Zone (PSZ) with a maximum dip of 62°. The most diagnostic structural features of increasing PSZ proximity were the occurrence of shear bands and reduction in mean quartz grain sizes. A change in composition to greater mica:quartz + feldspar, most markedly below c. 700 m MD, is inferred to result from either heterogeneous sampling or a change in lithology related to alteration. Major oxide variations suggest the fault-proximal Alpine Fault alteration zone, as previously defined in DFDP-1 core, was not sampled.</p

Atrial fibrillation genetic risk differentiates cardioembolic stroke from other stroke subtypes

AbstractObjectiveWe sought to assess whether genetic risk factors for atrial fibrillation can explain cardioembolic stroke risk.MethodsWe evaluated genetic correlations between a prior genetic study of AF and AF in the presence of cardioembolic stroke using genome-wide genotypes from the Stroke Genetics Network (N = 3,190 AF cases, 3,000 cardioembolic stroke cases, and 28,026 referents). We tested whether a previously-validated AF polygenic risk score (PRS) associated with cardioembolic and other stroke subtypes after accounting for AF clinical risk factors.ResultsWe observed strong correlation between previously reported genetic risk for AF, AF in the presence of stroke, and cardioembolic stroke (Pearson’s r=0.77 and 0.76, respectively, across SNPs with p &lt; 4.4 × 10−4 in the prior AF meta-analysis). An AF PRS, adjusted for clinical AF risk factors, was associated with cardioembolic stroke (odds ratio (OR) per standard deviation (sd) = 1.40, p = 1.45×10−48), explaining ∼20% of the heritable component of cardioembolic stroke risk. The AF PRS was also associated with stroke of undetermined cause (OR per sd = 1.07, p = 0.004), but no other primary stroke subtypes (all p &gt; 0.1).ConclusionsGenetic risk for AF is associated with cardioembolic stroke, independent of clinical risk factors. Studies are warranted to determine whether AF genetic risk can serve as a biomarker for strokes caused by AF.</jats:sec

Hydrothermal friction data of samples obtained from outcrops of the Mai'iu Fault, Papua New Guinae

General friction and rate and state friction data of powdered fault gouge samples derived from outcrops of the Mai'iu Fault, Papua New Guinae, which is one of the world's most rapidly slipping low-angle normal faults, The experiments show that gouges from the shallowest portion of the fault zone are predominantly weak and velocity-strengthening, while fault rocks deformed at greater depths are stronger and velocity-weakening. Evaluating the geodetic and friction results together with geophysical and microstructural evidence for mixed-mode seismic and aseismic slip at depth, we find that the Mai'iu fault is most likely strongly locked at depths of ~ 5 -16 km and creeping updip and downdip of this region. Our results suggest that the Mai'iu fault and other active low-angle normal faults can slip in large (M > 7) earthquakes despite near-surface interseismic creep on frictionally stable clay-rich gouges. The data is provided in 10 subfolders for 10 experiments/samples. Detailed information about the files in these subfolders as well as information on how the data is processed is given in the explanatory file Biemiller-et-al-2020-Data-Description.docx. Contact person is André Niemeijer - Assistant proffesor - [email protected] - https://www.uu.nl/staff/ARNiemeijer?t=

Understanding induced seismicity

Fluid injection–induced seismicity has become increasingly widespread in oil- and gas-producing areas of the United States (1–3) and western Canada. It has shelved deep geothermal energy projects in Switzerland and the United States (4), and its effects are especially acute in Oklahoma, where seismic hazard is now approaching the tectonic levels of parts of California. Unclear in the highly charged debate over expansion of shale gas recovery has been the role of hydraulic fracturing (fracking) in causing increased levels of induced seismicity. Opponents to shale gas development have vilified fracking as directly responsible for this increase in seismicity. However, this purported causal link is not substantiated; the predominant view is that triggering in the midwestern United States is principally a result of massive reinjection of energy-coproduced wastewaters. On page 1406 of this issue, Bao and Eaton (5) identify at least one example of seismicity developed from hydraulic fracturing for shale gas in the Alberta Basin

Understanding induced seismicity

Fluid injection–induced seismicity has become increasingly widespread in oil- and gas-producing areas of the United States (1–3) and western Canada. It has shelved deep geothermal energy projects in Switzerland and the United States (4), and its effects are especially acute in Oklahoma, where seismic hazard is now approaching the tectonic levels of parts of California. Unclear in the highly charged debate over expansion of shale gas recovery has been the role of hydraulic fracturing (fracking) in causing increased levels of induced seismicity. Opponents to shale gas development have vilified fracking as directly responsible for this increase in seismicity. However, this purported causal link is not substantiated; the predominant view is that triggering in the midwestern United States is principally a result of massive reinjection of energy-coproduced wastewaters. On page 1406 of this issue, Bao and Eaton (5) identify at least one example of seismicity developed from hydraulic fracturing for shale gas in the Alberta Basin