A Rare Functional Noncoding Variant at the GWAS-Implicated MIR137/MIR2682 Locus Might Confer Risk to Schizophrenia and Bipolar Disorder

Schizophrenia (SZ) genome-wide association studies (GWASs) have identified common risk variants in >100 susceptibility loci; however, the contribution of rare variants at these loci remains largely unexplored. One of the strongly associated loci spans MIR137 (miR137) and MIR2682 (miR2682), two microRNA genes important for neuronal function. We sequenced ∼6.9 kb MIR137/MIR2682 and upstream regulatory sequences in 2,610 SZ cases and 2,611 controls of European ancestry. We identified 133 rare variants with minor allele frequency (MAF) <0.5%. The rare variant burden in promoters and enhancers, but not insulators, was associated with SZ (p = 0.021 for MAF < 0.5%, p = 0.003 for MAF < 0.1%). A rare enhancer SNP, 1:g.98515539A>T, presented exclusively in 11 SZ cases (nominal p = 4.8 × 10−4). We further identified its risk allele T in 2 of 2,434 additional SZ cases, 11 of 4,339 bipolar (BP) cases, and 3 of 3,572 SZ/BP study controls and 1,688 population controls; yielding combined p values of 0.0007, 0.0013, and 0.0001 for SZ, BP, and SZ/BP, respectively. The risk allele T of 1:g.98515539A>T reduced enhancer activity of its flanking sequence by >50% in human neuroblastoma cells, predicting lower expression of MIR137/MIR2682. Both empirical and computational analyses showed weaker transcription factor (YY1) binding by the risk allele. Chromatin conformation capture (3C) assay further indicated that 1:g.98515539A>T influenced MIR137/MIR2682, but not the nearby DPYD or LOC729987. Our results suggest that rare noncoding risk variants are associated with SZ and BP at MIR137/MIR2682 locus, with risk alleles decreasing MIR137/MIR2682 expression

The genomic psychiatry cohort: Partners in discovery

The Genomic Psychiatry Cohort (GPC) is a longitudinal resource designed to provide the necessary population-based sample for large-scale genomic studies, studies focusing on Research Domain Criteria (RDoC) and/or other alternate phenotype constructs, clinical and interventional studies, nested case-control studies, long-term disease course studies, and genomic variant-to-phenotype studies. We provide and will continue to encourage access to the GPC as an international resource. DNA and other biological samples and diagnostic data are available through the National Institute of Mental Health (NIMH) Repository. After appropriate review and approval by an advisory board, investigators are able to collaborate in, propose, and co-lead studies involving cohort participants

Decadal variability in the Arctic Ocean shown in hydrochemical data

The recent distribution of Russian hydrochemical data collected from the Arctic Basin provides useful information on ocean interior variabilities. Among various chemical components, silicate is the most valuable for showing the boundary between the silicate-rich Pacific Water and the opposite Atlantic Water. Here, it is assumed that the silicate distribution receives minor influence from seasonal biological productivity and Siberian Rivers outflow. It shows a clear maximum around 100-m depth in the Canada Basin. The vertical gradient below 100 m provides information on the vertical motion of the upper boundary of the Atlantic Water at a decadal time scale: i.e., the boundary shifts upward (downward), as realized by the silicate reduction (increase) at a fixed depth, responding to a more intense (weaker) Polar Vortex or the positive (negative) phase of the Arctic Oscillation. This valuable hydrochemical data set has provided a tool for verifying Arctic Ocean models with decadal responses to atmospheric variabilities.An edited version of this paper was published by AGU. Copyright 2005, American Geophysical Union, Geophysical Research Letters, Issue 2

Price-list of hardy ornamental trees, hardy flowering shrubs, evergreens, roses, bulbs, herbaceous plants, fruits, etc. for parks, cemeteries, gardens and all public and private grounds /

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Price-list of hardy ornamental trees, hardy flowering shrubs, evergreens, roses, bulbs, herbaceous plants, fruits, etc. for parks, cemeteries, gardens and all public and private grounds.

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Price-list of hardy ornamental trees, hardy flowering shrubs, evergreens, roses, bulbs, herbaceous plants, fruits, etc. for parks, cemeteries, gardens and all public and private grounds /

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