A stable (Li, O) and radiogenic (Sr, Nd) isotope perspective on metasomatic processes in a subducting slab

Two distinct types of eclogites from the Raspas Complex (Ecuador), which can be distinguished based on petrography and trace element geochemistry, were analyzed for their stable (Li, O) and radiogenic (Sr, Nd) isotope signature to constrain metasomatic changes due to fluid-overprinting in metabasaltic rocks at high-pressure conditions and to identify fluid sources. MORB-type eclogites are characterized by a relative LREE depletion similar to MORB. High-pressure (HP) minerals from this type of eclogite have highly variable oxygen isotope compositions (garnet: + 4.1 to + 9.8 ‰; omphacite: + 6.1 to + 11.0 ‰; phengite: 8.7 to 10.4 ‰; amphibole: 6.2 to 10.1 ‰) and generally show equilibrium oxygen isotope fractionation. Initial 87Sr/86Sr isotope ratios are also variable (0.7037-0.7063), whereas εNd130Ma values (+ 8.3 to + 11.0) are relatively similar. Sr and O isotopic compositional differences among rocks on outcrop scale, the preservation of O isotopic compositions of low-temperature altered oceanic crust, and Sr-Nd isotopic trends typical for seafloor alteration suggest inheritance from variably altered oceanic crust. However, decreasing δ7Li values (-0.5 to -12.9 ‰) with increasing Li concentrations (11-94 ppm) indicate Li isotope fractionation by diffusion related to fluid-rock interaction. Li isotopes prove to be a very sensitive tracer of metasomatism, although the small effects on the Sr-Nd-O isotope systems suggest that the fluid-induced metasomatic event in the MORB-type eclogites was small-scale at low-water/rock ratios. This metasomatic fluid is thought to predominantly derive from in situ dehydration of MORB-type rocks. Zoisite eclogites, the second eclogite type from the Raspas Complex, are characterized by the presence of zoisite and enrichment in many incompatible trace elements compared to the MORB-type eclogites. The zoisite eclogites have a homogenous Sr-Nd isotopic signature (Initial 87Sr/86Sr = 0.7075-0.7081, εNd130Ma = -6.7 to -8.7), interpreted to reflect a metasomatic overprint. The isotopic signature can be attributed to the metasomatic formation of zoisite because associated zoisite veins are isotopically similar. Relatively homogenous O isotope values for garnet (10.9-12.3 ‰) omphacite (9.4 to 10.8 ‰), amphibole (10.0-10.1 ‰) and zoisite (10.5-11.9 ‰) and inter-mineral O isotopic disequilibria are consistent with a metasomatic overprint via open-system fluid input. Li concentrations (46-76 ppm) and δ7Li values of the zoisite eclogites overlap the range of the MORB-type eclogites. The large amount of fluid required for isotopic homogenization, combined with the results from fluid inclusion studies, suggests that deserpentinization played a major role in generating the metasomatic fluid that altered the zoisite eclogites. However, influence of a (meta)sedimentary source is required based on Sr-Nd isotope data and trace element enrichments. The significant geochemical variation in the various eclogites generated by interaction with metasomatic fluids has to be considered in attempts to constrain recycling at convergent margins

Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease

We identified rare coding variants associated with Alzheimer’s disease (AD) in a 3-stage case-control study of 85,133 subjects. In stage 1, 34,174 samples were genotyped using a whole-exome microarray. In stage 2, we tested associated variants (P<1×10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, an additional 14,997 samples were used to test the most significant stage 2 associations (P<5×10-8) using imputed genotypes. We observed 3 novel genome-wide significant (GWS) AD associated non-synonymous variants; a protective variant in PLCG2 (rs72824905/p.P522R, P=5.38×10-10, OR=0.68, MAFcases=0.0059, MAFcontrols=0.0093), a risk variant in ABI3 (rs616338/p.S209F, P=4.56×10-10, OR=1.43, MAFcases=0.011, MAFcontrols=0.008), and a novel GWS variant in TREM2 (rs143332484/p.R62H, P=1.55×10-14, OR=1.67, MAFcases=0.0143, MAFcontrols=0.0089), a known AD susceptibility gene. These protein-coding changes are in genes highly expressed in microglia and highlight an immune-related protein-protein interaction network enriched for previously identified AD risk genes. These genetic findings provide additional evidence that the microglia-mediated innate immune response contributes directly to AD development

Analysis of shared heritability in common disorders of the brain

ience, this issue p. eaap8757 Structured Abstract INTRODUCTION Brain disorders may exhibit shared symptoms and substantial epidemiological comorbidity, inciting debate about their etiologic overlap. However, detailed study of phenotypes with different ages of onset, severity, and presentation poses a considerable challenge. Recently developed heritability methods allow us to accurately measure correlation of genome-wide common variant risk between two phenotypes from pools of different individuals and assess how connected they, or at least their genetic risks, are on the genomic level. We used genome-wide association data for 265,218 patients and 784,643 control participants, as well as 17 phenotypes from a total of 1,191,588 individuals, to quantify the degree of overlap for genetic risk factors of 25 common brain disorders. RATIONALE Over the past century, the classification of brain disorders has evolved to reflect the medical and scientific communities' assessments of the presumed root causes of clinical phenomena such as behavioral change, loss of motor function, or alterations of consciousness. Directly observable phenomena (such as the presence of emboli, protein tangles, or unusual electrical activity patterns) generally define and separate neurological disorders from psychiatric disorders. Understanding the genetic underpinnings and categorical distinctions for brain disorders and related phenotypes may inform the search for their biological mechanisms. RESULTS Common variant risk for psychiatric disorders was shown to correlate significantly, especially among attention deficit hyperactivity disorder (ADHD), bipolar disorder, major depressive disorder (MDD), and schizophrenia. By contrast, neurological disorders appear more distinct from one another and from the psychiatric disorders, except for migraine, which was significantly correlated to ADHD, MDD, and Tourette syndrome. We demonstrate that, in the general population, the personality trait neuroticism is significantly correlated with almost every psychiatric disorder and migraine. We also identify significant genetic sharing between disorders and early life cognitive measures (e.g., years of education and college attainment) in the general population, demonstrating positive correlation with several psychiatric disorders (e.g., anorexia nervosa and bipolar disorder) and negative correlation with several neurological phenotypes (e.g., Alzheimer's disease and ischemic stroke), even though the latter are considered to result from specific processes that occur later in life. Extensive simulations were also performed to inform how statistical power, diagnostic misclassification, and phenotypic heterogeneity influence genetic correlations. CONCLUSION The high degree of genetic correlation among many of the psychiatric disorders adds further evidence that their current clinical boundaries do not reflect distinct underlying pathogenic processes, at least on the genetic level. This suggests a deeply interconnected nature for psychiatric disorders, in contrast to neurological disorders, and underscores the need to refine psychiatric diagnostics. Genetically informed analyses may provide important "scaffolding" to support such restructuring of psychiatric nosology, which likely requires incorporating many levels of information. By contrast, we find limited evidence for widespread common genetic risk sharing among neurological disorders or across neurological and psychiatric disorders. We show that both psychiatric and neurological disorders have robust correlations with cognitive and personality measures. Further study is needed to evaluate whether overlapping genetic contributions to psychiatric pathology may influence treatment choices. Ultimately, such developments may pave the way toward reduced heterogeneity and improved diagnosis and treatment of psychiatric disorders

Magmatic signatures and metasomatism in the high-pressure metamorphic Raspas Complex, Ecuador

The Raspas Complex is a high-pressure (HP) metamorphic complex in southwest Ecuador, representing an exhumed fragment of oceanic lithosphere. It is one of the few high-pressure ophiolites that contain the whole lithological sequence of a typical subducting slab and is therefore ideally suited to investigate how the different parts of the slab and their element budgets behave during subduction. The complex is subdivided into the Raspas Formation, which comprises eclogites, blueschists and metasediments, and the El Toro Formation, which consists of eclogite-facies, serpentinized peridotites [1]. Peak P-T conditions for eclogites and garnet-chloritoid-kyanite metapelites are very similar at about 2 GPa and 550-600 °C, and the age of metamorphism is around 130 Ma [2, 3]. Two distinct types of eclogites can be distinguished based on petrography and trace element geochemistry. The first eclogite type has a geochemical signature similar to mid-ocean ridge basalts (MORB) [3, 4], whereas the second eclogite type is characterized by the presence of zoisite and the relative enrichment in many incompatible trace elements (e.g. Th, U, Pb, LREE). Stable (Li, O) and radiogenic (Sr, Nd) isotopic compositions of the eclogites are used to constrain the effects of fluidinduced metasomatism in metabasaltic rocks at HP conditions and to identify fluid sources. For the MORB-type eclogites, Sr and O isotopic compositional differences on outcrop scale and Sr-Nd isotopic trends typical for seafloor alteration suggest inheritance from variably altered oceanic crust [5]. Lithium isotope compositions point to Li isotopic fractionation by diffusion-related fluid-rock interaction, demonstrating the high sensitivity of the Li isotope system to metasomatic effects. The zoisite eclogites are thought to have formed by a fluid-induced high-pressure metasomatic overprint, and their Sr-Nd isotopic compositions indicate a metasedimentary fluid component [5]. Within the serpentinized ultramafic rocks, which show evidence for prograde HP dehydration, metamorphosed dikes contain pargasitic amphibole, vesuvianite and rare Ca-rich garnet. Although the primary magmatic mineral assemblage has been replaced, elevated Al2O3 and CaO contents and correlations between Ni and MgO are similar to pyroxenites from orogenic ultramafic massifs. Positive Eu anomalies and up to 10" chondritic REE abundances point towards an origin as plagioclasebearing ultramafic cumulates based on similarities to cumulate gabbros and plagioclase wehrlites from abyssal plateaus and ultramafic massifs [6]. References: [1] Feininger, T. (1980): J. Petrol. 21:107-140. [2] Gabriele, P. et al. (2003): Eur. J. Mineral. 15:977-989. [3] John, T. et al. (2010): Contrib. Mineral. Petrol. 159:265-284. [4] Halama, R. et al. (2010): Geochim. Cosmochim. Acta 74:1636-1652. [5] Halama, R. et al. (2011): Chem. Geol. 281:151-166. [6] Borghini, G. et al. (2007): Lithos 94:210-229