Clinical OMICS

MAY-JUN 2017

Healthcare magazine for research scientists, labs, pathologists, hospitals, cancer centers, physicians and biopharma companies providing news articles, expert interviews and videos about molecular diagnostics in precision medicine

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38 Clinical OMICs May/June 2017 www.clinicalomics.com In the Lab The Psychiatric Genomics Consortium recent published new findings that show the first molecular evidence that genetic influences play a role in the risk of getting post-traumatic stress disorder (PTSD) after traumatic expe- riences. The report builds on previous findings that has shown genetic over- lap between PTSD and other mental disorders, such as schizophrenia. "We know from lots of data—from prisoners of war, people who have been in combat, and from rape vic- tims—that many people exposed to even extreme traumatic events do not develop PTSD. Why is that?" asked senior study investigator Karestan Koenen, Ph.D., professor of psychiatric epidemiology at Harvard T.H. Chan School of Public Health and head of the Global Neuropsychiatric Genom- ics Initiative of the Stanley Center for Psychiatric Research at Broad Insti- tute. "We believe that genetic variation is an important factor contributing to this risk or resilience." Interestingly, the new data also found that genetic risk for PTSD is strongest among women. Findings from the new study were published in Molecular Psychiatry in an arti- cle entitled "Largest GWAS of PTSD (N=20,070) Yields Genetic Overlap with Schizophrenia and Sex Differ- ences in Heritability." The new genome-wide association study (GWAS) brings together data from more than 20,000 people par- ticipating in 11 multiethnic studies around the world. The new findings build a strong case for the role of genetics in PTSD, which had been pre- viously documented on a smaller scale in studies of twins. Analysis of the data revealed that, among European American females, 29% of the risk for developing PTSD was influenced by genetic factors, which is comparable to that of other psychiatric disorders. In contrast, men's genetic risk for PTSD was substantially lower. The researchers also found strong evidence that people with a higher genetic risk for several mental dis- orders—including schizophrenia, and to a lesser extent bipolar and major depressive disorder—are also at higher genetic risk for developing PTSD after a traumatic event. "PTSD may be one of the most pre- ventable of psychiatric disorders," noted lead study investigator Laramie Duncan, Ph.D., instructor of psychia- try and behavioral sciences at Stanford University. "There are interventions effective in preventing PTSD shortly after a person experiences a traumatic event. But they are too resource inten- sive to give to everyone. Knowing more about people's genetic risk for PTSD may help clinicians target inter- ventions more effectively, and help us understand the underlying biological mechanisms." SolStock / Getty Images GWAS Uncovers Heritability of Post-Traumatic Stress Disorder greater than the group with later-onset pancreatitis. The two common genetic mutations found in the group with early-onset pancreatitis were cationic trypsinogen (PRSS1), found in 43% of patients; and chymotrypsin C (CTRC), found in 14%. "Overall, this research sheds light on a disease that not only affects adults, but an increasing number of children," said Dr. Giefer. "The findings provide us with an improved understanding of the genetic factors involved in early-onset pancreatitis, which will help the pediat- ric community to improve the evaluation and treatment process for patients." New Insights Arise from First Comprehensive Map of Subcellular Protein Localization An analysis of how proteins are arranged in a cell showed that a large portion of human proteins can be found in more than one location in a given cell. The study published in Science, was led by Emma Lundberg, associate profes- sor at KTH Royal Institute of Technology. The team generated more than 300,000 images to systematically resolve the spatial distribution of human proteins in cultivated cell lines, which were then mapped to cellular compartments and substructures with single-cell resolution. A total of 12,003 proteins targeted by 13,993 antibodies were classified into one or several of 30 cellular compart- ments and substructures, altogether defining the proteome of 13 major organelles. The organelles with the larg- est proteomes were the nucleus (6,930) and its substructures, such as bodies and speckles, and the cytosol (4,279). Interestingly, about one-half of the proteins are found in more than one compartment revealing a shared pool of proteins in functionally unrelated parts of the cell, a discovery that sheds new light on cellular complexity. n (continued from page 36)

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