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Boston, MA, United States

Massachusetts General Hospital is the original and largest teaching hospital of Harvard Medical School and a biomedical research facility located in the West End neighborhood of Boston, Massachusetts. It is the third oldest general hospital in the United States and the oldest and largest hospital in New England with 950 beds. Massachusetts General Hospital conducts the largest hospital-based research program in the world, with an annual research budget of more than $750 million. It is currently ranked as the #2 hospital in the United States by U.S. News & World Report. Wikipedia.


Background Findings from family and twin studies suggest that genetic contributions to psychiatric disorders do not in all cases map to present diagnostic categories. We aimed to identify specifi c variants underlying genetic eff ects shared between the fi ve disorders in the Psychiatric Genomics Consortium: autism spectrum disorder, attention defi cit-hyperactivity disorder, bipolar disorder, major depressive disorder, and schizophrenia. Methods We analysed genome-wide single-nucleotide polymorphism (SNP) data for the fi ve disorders in 33 332 cases and 27 888 controls of European ancestory. To characterise allelic eff ects on each disorder, we applied a multinomial logistic regression procedure with model selection to identify the best-fi tting model of relations between genotype and phenotype. We examined cross-disorder eff ects of genome-wide signifi cant loci previously identifi ed for bipolar disorder and schizophrenia, and used polygenic risk-score analysis to examine such eff ects from a broader set of common variants. We undertook pathway analyses to establish the biological associations underlying genetic overlap for the fi ve disorders. We used enrichment analysis of expression quantitative trait loci (eQTL) data to assess whether SNPs with cross-disorder association were enriched for regulatory SNPs in post-mortem brain-tissue samples. Findings SNPs at four loci surpassed the cutoff for genome-wide signifi cance (p< 5×10-8) in the primary analysis: regions on chromosomes 3p21 and 10q24, and SNPs within two L-type voltage-gated calcium channel subunits, CACNA1C and CACNB2. Model selection analysis supported eff ects of these loci for several disorders. Loci previously associated with bipolar disorder or schizophrenia had variable diagnostic specifi city. Polygenic risk scores showed cross-disorder associations, notably between adult-onset disorders. Pathway analysis supported a role for calcium channel signalling genes for all fi ve disorders. Finally, SNPs with evidence of cross-disorder association were enriched for brain eQTL markers. Interpretation Our fi ndings show that specifi c SNPs are associated with a range of psychiatric disorders of childhood onset or adult onset. In particular, variation in calcium-channel activity genes seems to have pleiotropic eff ects on psychopathology. These results provide evidence relevant to the goal of moving beyond descriptive syndromes in psychiatry, and towards a nosology informed by disease cause. Source


Patent
The Broad Institute Inc., Massachusetts General Hospital and Instituto Carlos Slim Of La Salud | Date: 2015-02-10

The present invention features a highly sensitive assay for detecting frameshift mutations for high throughput use. Also provided herein are methods for diagnosing or determining a predisposition for developing medullary cystic kidney disease type 1 (MCKD1) in a subject by detecting a frameshift mutation in the GC-rich variable number of tandem repeats (VNTR) sequence of the mucin 1 gene (MUC-1).


Patent
RaNA Therapeutics and Massachusetts General Hospital | Date: 2015-04-20

Aspects of the invention provide methods for selecting a candidate oligonucleotide for activating expression of a target gene. Further aspects of the invention provide methods of selecting a set of oligonucleotides that is enriched in oligonucleotides that activate expression of a target gene. Further aspects provide single stranded oligonucleotides that modulate gene expression and compositions and kits comprising the same. Methods for modulating gene expression using the single stranded oligonucleotides are also provided.


Patent
Siemens AG and Massachusetts General Hospital | Date: 2015-04-01

A magnetic resonance method and system are provided for generating real-time motion-corrected perfusion images based on pulsed arterial spin labeling (PASL) with a readout sequence such as a 3D gradient and spin echo (GRASE) image data acquisition block. The real-time motion correction is achieved by using a volumetric 3D EPI navigator that is provided during an intrinsic delay in the PASL sequence, which corrects for motion prospectively and does not extend the image data acquisition time as compared to a similar non-motion-corrected imaging procedure.


Patent
Siemens AG and Massachusetts General Hospital | Date: 2015-03-02

Disclosed herein is a framework for facilitating low power perfusion imaging. In accordance with one aspect, a gradient-modulated constant-adiabaticity radio frequency pulse sequence is generated. A labeling pulse from the pulse sequence is applied to a region of interest to label fluid supplying the region of interest and to acquire a tagged image. A control pulse from the pulse sequence may also be applied to the region of interest to acquire a control image. A perfusion image may then be generated using the tagged image and the control image.

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