Author Interviews, Genetic Research / 09.09.2019

MedicalResearch.com Interview with: Prof. Dominic Furniss, DM MA MBBCh FRCS Nuffield Department of Orthopaedics, Rheumatology, and Musculoskeletal Science University of Oxford MedicalResearch.com: What is the background for this study? Response: We knew that there was a genetic component to handedness. Twin studies estimated that around 25% of the variation in handedness seen in the human population is down to genetic factors. Genetic factors associated with left handedness had been shown in specific patient populations, but this study has found factors in the general population and correlated them with functional brain imaging to shed more light on this fascinating subject. We have used both genetic and imaging data from the UK Biobank study to discover genetic variants that are related to left handedness. We have correlated these variants with changes in brain imaging, in particular showing increased functional connectivity between the language processing areas of the brain in left handers. The genetic variants that are associated with left handedness are also near to genes involved in forming the internal skeleton of neurons, and important in brain development, suggesting that being left handed is in part caused by a difference in brain development. It is clear, however, that there are also many non-genetic influences on whether a person is left handed or not. In addition, we confirmed previous observations that being left handed is associated with other neurological problems, such as schizophrenia, and protective of others, such as Parkinson's disease, and showed that this is related to shared genetic factors, and likely reflects differences in brain development.  (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, JAMA, Ovarian Cancer, USPSTF / 28.08.2019

MedicalResearch.com Interview with: Dr. Carol Mangione, M.D., M.S.P.H., F.A.C.P. Division Chief of General Internal Medicine and Health Services Research Professor of Medicine Barbara A. Levey, MD, and Gerald S. Levey, MD, endowed chair in Medicine David Geffen School of Medicine University of California, Los Angeles (UCLA) Professor of public health at the UCLA Fielding School of Public Health.  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Every year, too many American women are faced with the challenge of dealing with a cancer diagnosis related to potentially harmful mutations of the BRCA1 and BRCA2 genes.  However, the Task Force found that there are several steps women can take to determine if they’re potentially at increased risk for BRCA gene mutations – and if genetic counseling and BRCA testing are needed. It is important to note that while some women can benefit from risk assessment, counseling, and testing, these services are not for everyone. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, Memory / 23.08.2019

MedicalResearch.com Interview with: Dr. Claude Alain PhD Senior Scientist Baycrest's Rotman Research Institute  MedicalResearch.com: What is the background for this study? Response: Adults carrying a gene associated with a higher risk of Alzheimer’s disease had a harder time accessing recently acquired knowledge, even though they didn’t show any symptoms of memory problems.  MedicalResearch.com: What are the main findings?  Response: Researchers found that older adults carrying a specific strain of the gene, apolipoprotein E4, otherwise known as APOE4, weren’t able to tap into information they had just learned to assist them on a listening test. These findings suggest greater difficulty for these individuals to access knowledge from their memory to guide their attention in ways that would have improved their performance. This work could lead to the development of new ways to detect individuals at risk. (more…)
Author Interviews, Breast Cancer, Brigham & Women's - Harvard, Genetic Research / 19.08.2019

MedicalResearch.com Interview with: Tengteng Wang, PhD, MSPH, MBBS Postdoctoral Research Fellow Department of Epidemiology Harvard T.H. Chan School of Public Health Channing Division of Network Medicine Brigham and Women's Hospital MedicalResearch.com: What is the background for this study? Response: Chronic inflammation is a key player in the development of multiple cancer types, including breast cancer. Aspirin is one of the major non-steroidal anti-inflammatory drugs (NSAIDs) which clearly has anti-inflammatory properties. Given this, substantial evidence from laboratory and population studies suggests that taking aspirin may reduce the risk of developing breast cancer. However, the association of aspirin use with death outcomes following breast cancer diagnosis remains inconclusive and inconsistent across studies. Therefore, we choose to focus on mortality outcomes in this paper and we hypothesized that the inconsistent results for aspirin in relation to mortality could be due to differences in the association by patients’ biological profiles, specifically DNA methylation profiles here.  (more…)
Author Interviews, Genetic Research, Heart Disease / 11.08.2019

MedicalResearch.com Interview with: Ambry GeneticsNancy Niguidula, MS, DPH Doctorate in Public Health in Toxicology Ambry Genetics   MedicalResearch.com: What is the background for this study? Response: The clinical presentations of many inherited cardiovascular conditions overlap; thus, genetic testing may clarify diagnoses, help with risk stratification, facilitate appropriate clinical management decisions, and aid in identifying asymptomatic, at-risk relatives. A large number of professional societies have developed practice guidelines and recommendations for genetic testing of cardiovascular diseases. These include international and collaborative expert panels that establish genetic screening and treatment recommendations by drawing on evidence-based medicine. To further strengthen the clinical utility of cardiovascular genetic testing, the American College of Medical Genetics and Genomics (ACMG) published a guideline for 59 genes with clinical actionability that should be reported if found on whole exome sequencing, even when unrelated to the testing indication. (more…)
Author Interviews, Cancer Research, Genetic Research / 08.08.2019

MedicalResearch.com Interview with: Upekha Liyanage MBBS |  PhD Student School of Medicine | University of Queensland Statistical Genetics Laboratory QIMR Berghofer Medical Research Institute MedicalResearch.com: What is the background for this study? What types of skin cancers are linked to these genes? Response: Basal cell carcinoma (BCC) and squamous cell carcinoma (SCC) collectively referred to as “keratinocyte cancers” are the commonest forms of cancers of the skin. Although these cancers are less aggressive than melanoma, due to their large numbers, they pose a significant burden to the healthcare expenditure. Also, these cancers are relatively understudied when compared with melanoma. Notably, BCC and SCC are not routinely reported in cancer registries. In Australia, Medicare data are used to estimate the incidence and costs associated with these cancers. Expenditure in Australia for the diagnosis, treatment and pathology, almost exceeds $700 million for both BCC and squamous cell carcinoma. In Unites States, the average annual cost for skin cancer including melanoma is approximately $8.1 billion. Previous research has led to identification of 29 BCC and 11 squamous cell carcinoma genetic risk variants and 7 of them overlap with both BCC and SCC risk. So, to strengthen the preventive efforts and to reveal new therapeutics, it is very timely and critical to explore more on the genetic susceptibility of these deadly cancers. We analysed ~48,000 cancer cases with ~630,000 skin cancer free controls from European ancestry population in Australia, UK and USA.  (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 31.07.2019

MedicalResearch.com Interview with: Dr. Amy Dunn, PhD Kaczorowski lab The Jackson Laboratory  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Environmental factors, such as a poor diet, are known risk factors for Alzheimer’s disease. But the mechanisms are complex, and it is not known how such environmental perturbations interact with individual genetic variation to confer disease risk. Previous studies have not adequately addressed how the combination of genetic variant and environmental factors combine to alter cognitive response to a poor diet. To investigate gene-by-environment interactions, we fed either a normal diet or a high-fat diet to a genetically diverse Alzheimer’s disease mouse model population starting at six months of age and monitored metabolic and cognitive function. We observed accelerated working memory decline in the mice on the high-fat diet after eight weeks, with substantial gene-by diet effects on both cognitive and metabolic traits. Metabolic dysfunction was more closely related to cognitive function in mice carrying Alzheimer’s mutations than in those without. Interestingly, the high-fat diet affected metabolic function differently in female versus male mice.  (more…)
Author Interviews, Genetic Research, Heart Disease, Imperial College, JAMA / 12.07.2019

MedicalResearch.com Interview with: Ben Cordon, PhD NIHR Post-doctoral Academic Clinical Fellow Specialist Registrar training in cardiology  James S. Ware, PhD, MRCP  Reader in Genomic Medicine Group head within the Cardiovascular Genetics & Genomics Unit Imperial College London     MedicalResearch.com: What is the background for this study?   Response: Non-ischaemic dilated cardiomyopathy is a common cause of heart failure and carries the risk of life-threatening ventricular arrhythmia. An implantable cardioverter defibrillator (ICD) can be life-saving in this condition. However, the decision to implant an ICD is not one that can be taken lightly - ICD insertion carries its own risks, such as infection or inappropriate shocks, and our ability to predict who will benefit from a device is currently far from perfect. Genetic sequencing is affordable and widely available and for DCM, like many diseases, it is hoped that genetic stratification may one day help deliver personalised management. In DCM, variants in the Lamin A/C gene for example are known to cause a phenotype with early and severe arrhythmias and, as a result, international guidelines advocate a lower threshold for ICD insertion in these patients. However, Lamin A/C is an infrequent cause of DCM. The commonest known genetic cause of DCM are protein-truncating variants in the gene encoding Titin (TTNtv), accounting for ~15% of DCM cases. We wanted to know if this group had a higher risk of arrhythmia than the general DCM population. Earlier work from our group on this topic found that patients with TTNtv-associated DCM were more likely to have a clinical history of arrhythmia (composite of atrial and ventricular arrhythmia, including NSVT), at the time of their initial DCM diagnosis. But it was unclear if this was driven by ventricular arrhythmia, atrial arrhythmia, or both or if it would translate into a long-term risk of potentially dangerous ventricular arrhythmia of the sort for which an ICD can be life-saving. In another study we analysed a larger cohort of ambulant DCM patients but did not find an increased risk of ventricular arrhythmia – but this was a relatively low-risk group, with comparatively mild symptoms (NHYA I/II heart failure) and moderately impaired LV function. As a result, the overall arrhythmic event rate was low, meaning that the power to detect differences between the TTNtv and non-TTNtv groups was reduced. (more…)
Author Interviews, Cost of Health Care, Genetic Research, Personalized Medicine / 02.07.2019

Dr. Winegarden
Dr. Winegarden

MedicalResearch.com Interview with:

Wayne Winegarden, Ph.D.
Director, Center for Medical Economics and Innovation
Pacific Research Institute

MedicalResearch.com:  What is the background for this poll? Would you tell us a little about the Center for Medical Economics and Innovation? 

Response: Recent press reports have focused on how extensive innovative gene therapies can be.  PRI was interested in learning where Americans stand on these cures of the future, and commission a new national opinion survey to find out.

The Center for Medical Economics and Innovation is a new center launched by PRI this spring to research and advance policies showing how a thriving biomedical and pharmaceutical sector benefits both patients and economic growth. Medical innovation is an important driver of economic growth, responsible for over $1.3 trillion in economic activity each year. As the Milken Institute has found, every job in the biomedical sphere supports another 3.3 jobs elsewhere in the economy.

Among the activities of the Center – which can be accessed at www.medecon.org – are providing free-market analysis to evaluate current policy proposals, producing easy-to-understand data and analysis on current trends in medical science, breaking down complex issues like pharmaceutical and biomedical pricing structures, and demonstrating the benefits that market-based reforms can offer patients and the U.S. health care system.  (more…)

Author Interviews, Cancer Research, Genetic Research, Pediatrics / 24.06.2019

MedicalResearch.com Interview with: Philip J. Lupo, PhD, MPH Co-Director, Childhood Cancer Epidemiology and Prevention Program, Texas Children's Cancer Center Associate Professor, Department of Pediatrics Section of Hematology-Oncology, Member, Dan L. Duncan Comprehensive Cancer Center Baylor College of Medicine Adjunct Associate Professor, Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences University of Texas School of Public Health   MedicalResearch.com: What is the background for this study?   Response: While cancer risk in children with certain chromosomal defects like Down syndrome is well established, much less is known for children with birth defects where there is no known genetic cause, sometimes called non-chromosomal defects. Non-chromosomal defects, as a group, affect more children, but one of the primary challenges of understanding risk among these children is that limited sample sizes make studying specific defects, like spina bifida, more difficult. Because of that, we gathered data from birth, birth defect, and cancer registries across Texas, Arkansas, Michigan, and North Carolina to generate a birth cohort of more than 10 million children born between 1992 and 2013. We looked at diagnoses of cancer until 18 years of age to determine differences in cancer risk between those with and without birth defects. (more…)
Author Interviews, Environmental Risks, Genetic Research, Prostate Cancer / 20.06.2019

MedicalResearch.com Interview with: Emanuela Taioli, MD, PhD, Director of the Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai Asociate director for Population Science Tisch Cancer Institute  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: An excess incidence of prostate cancer has been identified among World Trade Center responders. We wanted to study if this excess was associated with exposure to WTC dust The results suggest that respiratory exposure to WTC dust can induce inflammatory and immune responses in prostate tissue. Chronic inflammation could facilitate prostate cancer development Taken together, our results suggest that World Trade Center prostate cancer cases have a distinct gene expression pattern that may be the result of exposure to specific carcinogens during the WTC attacks. WTC dust-exposed rat prostate displayed unique changes in gene expression and immune cell infiltrates after acute dust exposure, suggesting that the effect of exposure may be measured locally in target organs such as prostate. In addition, some of the genes overexpressed in rat normal prostates as a consequence of exposure are also overexpressed in human prostate cancer tissues, suggesting a link between exposure, local immune dysregulation, and prostate cancer development (more…)
Author Interviews, Biomarkers, Genetic Research, Infections, NEJM, UCSF / 13.06.2019

MedicalResearch.com Interview with: Dr. Charles Chiu, M.D./Ph.D. Professor, Laboratory Medicine and Medicine / Infectious Diseases Director, UCSF-Abbott Viral Diagnostics and Discovery Center Associate Director, UCSF Clinical Microbiology Laboratory UCSF School of Medicine MedicalResearch.com: What is the background for this study? Would you describe what is meant by metagenomic sequencing? Response: Metagenomic next-generation sequencing (mNGS) is the use of technology to generate millions of sequence reads to diagnose infection sin patients by characterizing the full range of potential pathogens (bacteria, viruses, fungi, and parasites) in a single sample. Although shown to be a promising diagnostic tool for  infectious diseases in case reports and limited case series (Chiu and Miller Nature Reviews Genetics 20, 341-355 (2019)), to date the “real-life” utility of this approach for patient care has hitherto not been demonstrated.  This study is the first prospective, multi-center study of clinical mNGS testing for the diagnosis of neurological infections in acutely ill hospitalized patients presenting with meningitis and/or encephalitis. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, Novartis / 03.06.2019

MedicalResearch.com Interview with: Fabrice André, MD, PhD Research director and head of INSERM Unit U981 Professor in the Department of Medical Oncology Institut Gustave Roussy in Villejuif, France Global SOLAR-1 Principal Investigator. MedicalResearch.com: What is the background for this study? How does Piqray®  differ from other treatments for this type of advanced breast cancer? 
  • The US Food and Drug Administration (FDA) approved Piqray® (alpelisib, formerly BYL719) in combination with fulvestrant for the treatment of postmenopausal women, and men, with hormone receptor positive, human epidermal growth factor receptor-2 negative (HR+/HER2-), PIK3CA-mutated, advanced or metastatic breast cancer, as detected by an FDA-approved test after disease progression following an endocrine-based regimen.
  • Piqray is the first and only combination treatment with fulvestrant specifically for postmenopausal women, and men, with HR+/HER2- advanced or metastatic breast cancer with a PIK3CA mutation following progression on or after an endocrine-based regimen, bringing a biomarker-driven therapy option to this population for the first time.
  • Advanced breast cancer is incurable, and patients with all types need more treatment options. With this approval, physicians can now use an FDA-approved test to determine if their patients’ HR+/HER2- advanced breast cancer has a PIK3CA mutation and may be eligible for treatment with Piqray plus fulvestrant combination therapy. 
(more…)
Author Interviews, Clots - Coagulation, Duke, Genetic Research, Heart Disease, JAMA / 30.05.2019

MedicalResearch.com Interview with: Thomas J. Povsic, MD, PhD Interventional Cardiologist Duke Clinical Research Institute Duke University School of Medicine Durham, North Carolina  MedicalResearch.com: What is the background for this study?  Response: The background for this study is that it is unknown how mandatory reporting of CYP2C19 metabolizer status affects how doctors treat patients or to what degree provision of this information would affect choice of a P2Y12 inhibitor within a clinical trial. As part of the GEMINI-ACS trial, all patients underwent CYP2C19 metabolizer testing.  This trial enrolled patients with a recent acute coronary syndrome and randomized them to aspirin or a low dose of rivaroxaban.  All patients were also to be treated with ticagrelor or clopidogrel, which was at the discretion of the investigator.  Investigators were given information regarding the CYP2C19 metabolizer status about a week after randomization.  Importantly prior to randomization, all investigators were asked how they expected to use this information, and then we followed what they actually did. (more…)
Author Interviews, Genetic Research / 17.05.2019

MedicalResearch.com Interview with: Tove Fall PhD Senior author of the study Associate Professor in Epidemiology Department of Medical Sciences and the Science for Life Laboratory Uppsala University  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Dog ownership is common in the Western society but little is known about what actually makes people get a dog. We conducted a twin study to understand whether the genetic make-up has an influence on this choice. We found that more than 50% of the differences in dog ownership is explained by genetic variants.  (more…)
Author Interviews, Genetic Research, PNAS / 02.05.2019

MedicalResearch.com Interview with: Dr. Casey Trimmer, PhD Geneticist, was a post-doctoral fellow at the Monell Center when the research was conducted MedicalResearch.com: What is the background for this study?   Response: We detect odors using 400 different types of sensor proteins, called olfactory receptors, in our noses. An odor molecule activates a specific combination of these receptors, and this pattern of activation gives us information on what we're smelling--whether its floral or smoky, intense or weak, and how much we like it. However, how the system translates receptor activation to these perceptual features is largely unknown. Here, we take advantage of the extensive genetic variation in the OR gene family to understand the contribution of individual ORs to odor perception. By studying cases where the function of a particular OR is lost, we can examine what kinds of perceptual alterations occur, allowing us to link receptor to odor and understand what kind of information the receptor is encoding. Data linking genetic variation to perceptual changes exist for only 5 ORs. Here, we examined the perceived intensity and pleasantness of 68 odors in 332 participants. We used next-generation genome sequencing to identify variants in 418 OR genes and conducted a genetic association analysis to relate this variation to differences in odor perception. We then use a cell-based assay to examine receptor function and investigate the mechanisms underlying our associations. Finally, we examined the contribution of single OR genotype, genetic ancestry, age, and gender to variations in odor perception. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA, Technology / 30.04.2019

MedicalResearch.com Interview with: Steven J.M. Jones, Professor, FRSC, FCAHS Co-Director & Head, Bioinformatics Genome Sciences Centre British Columbia Cancer Research Centre Vancouver, British Columbia, Canada and Jasleen Grewal, BSc.Genome Sciences CentreBritish Columbia Cancer Research CentreVancouver, British Columbia, CanadaJasleen Grewal, BSc. Genome Sciences Centre British Columbia Cancer Research Centre Vancouver, British Columbia, Canada MedicalResearch.com: What is the background for this study? Response: Cancer diagnosis requires manual analysis of tissue appearance, histology, and protein expression. However, there are certain types of cancers, known as cancers of unknown primary, that are difficult to diagnose based purely on their appearance and a small set of proteins. In our precision medicine oncogenomics program, we needed an accurate approach to confirm diagnosis of biopsied samples and determine candidate tumour types for where the primary site of the cancer was uncertain.  We developed a machine learning approach, trained on the gene expression data of over 10,688 individual tumours and healthy tissues, that has been able to achieve this task with high accuracy. Genome sequencing offers a high-resolution view of the biological landscape of cancers. RNA-Seq in particular quantifies how much each gene is expressed in a given sample. In this study, we used the entire transcriptome, spanning 17,688 genes in the human genome, to train a machine learning method for cancer diagnosis. The resultant method, SCOPE, takes in the entire transcriptome and outputs an interpretable confidence score from across a set of 40 different cancer types and 26 healthy tissues.  (more…)
Author Interviews, Genetic Research, Nutrition, Sugar / 28.04.2019

MedicalResearch.com Interview with: Dr Daniel Hwang PhD Postdoctoral Research Fellow The University of Queensland Diamantina Institute MedicalResearch.com: What is the background for this study?   Response: The aim of the this study is to understand the genetic basis of human taste perception. In this international collaboration project, we started by collecting sensory data from twins in the Australia and USA since 2003. Based on the difference in the genetic relatedness between identical and non-identical twins, our previous studies have quantified the amount of genetic influence on sweet taste perception (https://doi.org/10.1017/thg.2015.42) as well as the other sensory phenotypes (https://doi.org/10.1093/chemse/bjs070).  (more…)
Author Interviews, Dental Research, Genetic Research / 28.04.2019

MedicalResearch.com Interview with: Katrina Scurrah PhD Senior Research Fellow (Biostatistician), Twins Research Australia, and Melbourne School of Population and Global Health, The University of Melbourne and Honorary Fellow, Murdoch Childrens Research Institute. MedicalResearch.com: What is the background for this study? Response: Oral health is an important component of general health and yet dental caries (decay) is still common in children (affecting up to one in three 5-6 year old children in Australia). Although we know that some genetic and lifestyle factors (such as diet) are important risk factors for caries, the relative importance of these is still unclear.  Risk factors from pregnancy and very early childhood (even before teeth appear) might also be important. This study is the first to include prospectively measured data on health and well-being from pregnancy, birth and early childhood in a study of twin children. We analysed data from a cohort of 172 pairs of twin children to assess the effects of genes and environment on susceptibility to dental caries at six years-of-age. (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA, Lipids / 25.04.2019

MedicalResearch.com Interview with: Florian Kronenberg, MD Division of Genetic Epidemiology Department of Medical Genetics, Molecular and Clinical Pharmacology Medical University of Innsbruck, Innsbruck, Austria MedicalResearch.com: What is the background for this study? Response: Lp(a) is one of the most prevalent lipoprotein risk factors for cardiovascular disease. Roughly 20% of the general Caucasian population have concentrations above 50 mg/dL and the 10% with the highest concentrations have a 2 to 3-fold increased risk for myocardial infarction. There is strong evidence from genetic studies that high Lp(a) concentrations are causally related to cardiovascular outcomes. Until recently there was no drug available which lowers Lp(a) without any effects on other lipoproteins. This has recently changed by the development of drugs that block the production of Lp(a) in an impressive way. These drugs have to be studied in randomized controlled trials whether they not only lower Lp(a) concentrations but also cardiovascular outcomes. For the planning of such studies it is crucial to estimate the amount of Lp(a) lowering required to show a clinical benefit. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research, Surgical Research / 22.04.2019

MedicalResearch.com Interview with: Valentine N. Nfonsam, MD, MS, FACS Associate Professor of Surgery Program Director, General Surgery Residency Colon and Rectal Surgery Division of Surgical Oncology University of Arizona, Tucson  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The overall incidence of colon cancer in the United states has gone down in the last few decades. However, there has been a significant increase in the incidence of sporadic colon cancer is young patients (<50 years old). The etiology of this phenomenon is likely multi-factorial. These young patients do present with more advanced disease and with aggressive features. We demonstrated in our study that the colon cancer tumor biology was different between young and older patients. We also singled out a particular gene, Cartilage oligomeric Matrix Protein (COMP) which was significantly over-expressed in young patients and demonstrated its role in cancer proliferation and metastasis and also its potential as a prognostic biomarker since we were able to detect it in plasma. (more…)
Author Interviews, Depression, Genetic Research, JAMA / 19.04.2019

MedicalResearch.com Interview with: Dr Kimberley Kendall MBBCh Wellcome Trust Clinical Research Fellow Professor James Walters MRC Centre for Neuropsychiatric Genetics and Genomics Professor, Division of Psychological Medicine and Clinical Neurosciences Cardiff University   MedicalResearch.com: What is the background for this study? Response: Copy number variants (CNVs) are the deletion or duplication of large sections of DNA. Large, rare CNVs have been shown to increase the risk of neurodevelopmental disorders including autism spectrum disorder (ASD), intellectual disability (ID), attention deficit/hyperactivity disorder (ADHD) and schizophrenia. However, the impact of these CNVs on risk of depression was unclear from the existing literature. (more…)
Author Interviews, Cancer Research, Genetic Research / 18.04.2019

MedicalResearch.com Interview with: Rachid Karam, PhD Director, Ambry Translational Genomics Lab Ambry Genetics  MedicalResearch.com: What is the background for this study? Response: DNA genetic testing (DGT) for hereditary cancer genes is now a well accepted clinical practice; however, the interpretation of DNA variation remains a challenge to laboratories and medical providers. RNA genetic testing (RGT) as a supplement to DGT is a means to clarify the clinical actionability of variants in hereditary cancer genes, improving our ability to accurately apply known strategies for cancer risk reduction. (more…)
Author Interviews, Genetic Research, Microbiome / 13.04.2019

MedicalResearch.com Interview with: Kyung Mo Kim Senior research scientist Korea Polar Research Institute. Professor Gustavo Caetano-Anollés Carl R. Woese Institute for Genomic Biology University of Illinois Arshan Nasir Distinguished Fellow Los Alamos National Laboratory in New Mexico MedicalResearch.com: What is the background for this study? What are the main findings? Response: Horizontal gene transfer is the process by which unrelated microorganisms can exchange genes. The famous examples would be transfer of antibiotic resistance genes among bacteria that renders many commercially expensive antibiotics useless. From an evolutionary point of view, it complicates our understanding of how bacteria are related since even distantly-related bacteria can share genes and then cluster together on evolutionary trees. Thus better understanding horizontal evolution is important for both public health and our basic understanding of microbial taxonomy and evolution. There are some excellent existing methods of HGT detection that compare DNA features (e.g. GC%, codon usage) or statistical similarity between genomes to identify foreign genes. However, these methods work better to identify recently transferred genes. Transfers that happened millions or billions of years ago cannot be reliably detected since DNA sequences evolve over time during which foreign DNA can become more host-like. That is why we focused our attention on utilizing approaches that are based on sound evolutionary principles. If a gene is horizontally acquired, then a phylogenetic tree of that gene will be different from the reference or known tree of the organisms. The true phylogenetic tree of organisms describes how organisms have descended from a common ancestor through inheritance of genes. If a gene is acquired from a source outside the parents or from an unrelated organism, then there will be a conflict between gene tree and the reference/known species tree. This conflict can be indication of HGT. (more…)
Author Interviews, Epilepsy, Genetic Research, JAMA, Pediatrics / 12.04.2019

MedicalResearch.com Interview with: Dr. Ahmad Abou Tayoun, PhD Clinical Molecular Geneticist Director of the Genetics Laboratory Al Jalila Children’s United Arab Emirates MedicalResearch.com: What is the background for this study?   Response: In this study, we provide data in favor of using an exome-based testing approach, where parental samples can be readily accessible, for early onset epilepsy patients. The exome test includes all coding genes in the human genome. Although we perform exome sequencing on those patients, we demonstrate that a first tier analysis should include targeted interpretation of ~100 genes strongly associated with the disease. This analysis provides diagnoses in ~11% of the patients. Follow up parental testing on a limited number of patients (n=15) that had inconclusive results, revealed de novo (new mutations) variant status, leading to upgrade to positive reports in 7 patients and adding ~5% to the overall diagnostic yield. (more…)
Author Interviews, Cancer Research, Genetic Research / 08.04.2019

MedicalResearch.com Interview with: Eunhee Yi, Ph.D. Postdoctoral Associate The Jackson Laboratory MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Recurrence after therapy for glioblastoma (GBM) is unavoidable. There are substantial differences among the cells of GBM tumors in the abundance and types of genetic materials. This heterogeneity is a major driver of therapy failure and disease progression. We previously reported that extrachromosomal DNA (ecDNA) elements, which reside outside the linear genome and represent a mechanism to amplify and activate oncogenes, is a potential cause of the increasing genetic diversity in GBM. Our current study is focused on the development of a novel cytogenetic tool to visualize ecDNA to visualize the behavior of these elements in live cells. We have leveraged the unique properties of ecDNA to develop a CRISPR-based “ecDNA tracing toolbox (EDTB)”.  (more…)
Alcohol, Author Interviews, Genetic Research, Nature, University of Pennsylvania / 05.04.2019

MedicalResearch.com Interview with: Henry R. Kranzler, MD Professor of Psychiatry Perelman School of Medicine University of Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: Alcohol consumption and alcohol use disorder (AUD) are moderately heritable traits.  To date, genome-wide association studies (GWAS) have not examined these traits in the same sample, which limits an assessment of the extent to which genetic variation is unique to one or the other or shared. This GWAS examined a large sample (nearly 275,000 individuals) from the U.S. Veterans Affairs Million Veteran Program (MVP) for whom data on both alcohol consumption and alcohol use disorder diagnoses were available from an electronic health record.  We identified 18 genetic variants that were significantly associated with either alcohol consumption, AUD, or both. Five of the variants were associated with both traits, eight with consumption only, and five with alcohol use disorder only.  (more…)
Author Interviews, Diabetes, Genetic Research, JAMA, Mental Health Research, Schizophrenia / 03.04.2019

MedicalResearch.com Interview with: Prof Sabine Bahn MD PhD MRCPsych FRSB Cambridge Centre for Neuropsychiatric Research Jakub Tomasik, PhD Department of Chemical Engineering and Biotechnology University of Cambridge   MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Schizophrenia patients are at increased risk of impaired glucose metabolism, yet the comorbidity between the two conditions cannot be fully explained by known risk factors such as obesity, smoking, stress or antipsychotic medication. Previous family and genome-wide studies have suggested that the co-occurrence between schizophrenia and impaired glucose metabolism might be due to shared genetic factors, as exemplified by increased risk of diabetes in first-degree relatives of schizophrenia patients, but the biological mechanisms underlying this association remain unknown. We examined the association between insulin resistance, schizophrenia polygenic risk and response to treatment in 58 drug-naive schizophrenia patients and 58 matched healthy individuals while controlling for a range of demographic (age, gender, body mass index), lifestyle (smoking, alcohol and cannabis use) and clinical (psychopathology scores, treatment drug) factors. We found that insulin resistance, a key feature contributing to the development of type 2 diabetes, significantly correlated with schizophrenia polygenic risk score in patients, with higher genetic risk of schizophrenia associated with increased insulin resistance. Furthermore, we found that patients with higher insulin resistance were more likely to switch medication during the first year of treatment, which implies lower clinical response.  (more…)
Author Interviews, Diabetes, Genetic Research, Heart Disease, Nature / 02.04.2019

MedicalResearch.com Interview with: Eirini Marouli William Harvey Research Institute Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London MedicalResearch.com: What is the background for this study?   Response: Epidemiological studies suggest that shorter stature is associated with increased risk of coronary artery disease (CAD) or type 2 diabetes (T2D). It is not clear though whether these associations are causal or there are other factors mediating these effects. When randomized trials are inappropriate or impossible, we can use Mendelian Randomisation as a good alternative to study the causal relationship between a trait and a disease. Here, we examined over 800 places in the human genome known to be associated with adult height and evaluated how genetically predicted height can affect the risk of CAD or T2D. Furthermore, we evaluated the role of several risk factors including, cholesterol, triglycerides, blood pressure, body mass index, fat percentage, socio-economic parameters including education and income as well as lung function. Lung function was assessed by spirometry measures including FEV1: forced expiratory volume in 1 second, FVC: forced vital capacity. (more…)
Author Interviews, Endocrinology, Genetic Research / 24.03.2019

MedicalResearch.com Interview with: Emily J. Gallagher, MD Assistant Professor of Medicine Endocrinology, Diabetes and Bone Disease Icahn School of Medicine at Mount Sinai  MedicalResearch.com: What is the background for this study? Response: Multiple Endocrine Neoplasia Syndrome Type 2 (MEN2) is an inherited endocrine disorder characterized by the development of pheochromocytoma, medullary thyroid carcinoma (MTC) and parathyroid tumors. It occurs due to activating missense variants in the RET gene. The estimated prevalence of MEN2 is 1 per 30,000 in the general population. Through a collaboration between The Center for Genomic Health, the Charles Bronfman Institute for Personalized Medicine, and the Division of Endocrinology at Mount Sinai, our aim was to investigate the prevalence and clinical manifestations of pathogenic RET variants in the multi-ethnic BioMe Biobank. The BioMe Biobank is an electronic health record-linked biobank with exome sequencing data available for more than 30,000 patients recruited across The Mount Sinai Health System. (more…)