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. 
Author Interviews, Cancer Research, Dermatology / 14.08.2019

MedicalResearch.com Interview with: [caption id="attachment_50843" align="alignleft" width="160"]Dr Alessia Visconti, PhD Department of Twin Research King's College London, London  Dr. Visconti[/caption] Dr Alessia Visconti, PhD Department of Twin Research King's College London, London MedicalResearch.com: What is the background for this study? Response: We know from previous studies that the body site where melanoma skin cancer develops varies according to sex, with men having melanoma more often on the head, neck, and trunk, and women on the legs. The body site where moles, a major risk factor for melanoma development, are more abundant also varies according to sex, at least in childhood, with boys having more moles on the head, neck, and trunk, and girls on the legs.
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.
Alzheimer's - Dementia, Author Interviews, Genetic Research / 31.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50502" align="alignleft" width="151"] Dr. Dunn[/caption] 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. 
Author Interviews, Genetic Research, Heart Disease, Imperial College, JAMA / 12.07.2019

MedicalResearch.com Interview with: [caption id="attachment_50228" align="alignleft" width="112"]Ben Cordon, PhD NIHR Post-doctoral Academic Clinical Fellow Specialist Registrar training in cardiology Dr. Cordon[/caption] Ben Cordon, PhD NIHR Post-doctoral Academic Clinical Fellow Specialist Registrar training in cardiology  [caption id="attachment_50229" align="alignleft" width="112"]James S. Ware, PhD, MRCP  Reader in Genomic Medicine Group head within the Cardiovascular Genetics & Genomics Unit Imperial College London Dr. Ware[/caption] James SWarePhD, 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.
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. 

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

MedicalResearch.com Interview with: [caption id="attachment_49846" align="alignleft" width="143"]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 Dr. Lupo[/caption] 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.
Author Interviews, Environmental Risks, Genetic Research, Prostate Cancer / 20.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49841" align="alignleft" width="130"]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 Dr. Taioli[/caption] 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
Author Interviews, Biomarkers, Genetic Research, Infections, NEJM, UCSF / 13.06.2019

MedicalResearch.com Interview with: [caption id="attachment_49751" align="alignleft" width="150"]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 Dr. Chiu[/caption] 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.
Author Interviews, Clots - Coagulation, Duke, Genetic Research, Heart Disease, JAMA / 30.05.2019

MedicalResearch.com Interview with: [caption id="attachment_49440" align="alignleft" width="133"]Thomas J. Povsic, MD, PhDInterventional CardiologistDuke Clinical Research InstituteDuke University School of MedicineDurham, North Carolina  Dr. Povsic[/caption] 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.
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. 
Author Interviews, Genetic Research, PNAS / 02.05.2019

MedicalResearch.com Interview with: [caption id="attachment_48961" align="alignleft" width="200"]Dr. Casey Trimmer, PhDGeneticist, was a post-doctoral fellow at the Monell Center when the research was conducted Dr. Trimmer[/caption] 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.
Author Interviews, Cancer Research, Genetic Research, JAMA, Technology / 30.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48863" align="alignleft" width="132"]Steven J.M. Jones, Professor, FRSC, FCAHSCo-Director & Head, BioinformaticsGenome Sciences CentreBritish Columbia Cancer Research CentreVancouver, British Columbia, Canada Dr. Jones[/caption] 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. 
Author Interviews, Dental Research, Genetic Research / 28.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48895" align="alignleft" width="200"]Katrina Scurrah MDMelbourne School of Population and Global Health Dr. Scurrah[/caption] 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.
Author Interviews, Genetic Research, Heart Disease, JAMA, Lipids / 25.04.2019

[caption id="attachment_48766" align="alignleft" width="130"]Florian Kronenberg Dr. Kronenberg[/caption] 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.
Author Interviews, Cancer Research, Colon Cancer, Genetic Research, Surgical Research / 22.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48735" align="alignleft" width="133"]Valentine N. Nfonsam, MD, MS, FACSAssociate Professor of SurgeryProgram Director, General Surgery ResidencyColon and Rectal SurgeryDivision of Surgical OncologyUniversity of Arizona, Tucson Dr. Nfonsam[/caption] 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.
Author Interviews, Depression, Genetic Research, JAMA / 19.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48629" align="alignleft" width="150"]Dr Kimberley Kendall MBBChWellcome Trust Clinical Research Fellow Dr. Kendall[/caption] Dr Kimberley Kendall MBBCh Wellcome Trust Clinical Research Fellow [caption id="attachment_48630" align="alignleft" width="150"]Professor James WaltersMRC Centre for Neuropsychiatric Genetics and GenomicsProfessor, Division of Psychological Medicine and Clinical Neurosciences Prof. Walters[/caption] 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.
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.
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.
Author Interviews, Epilepsy, Genetic Research, JAMA, Pediatrics / 12.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48481" align="alignleft" width="200"]Dr. Ahmad Abou Tayoun, PhDClinical Molecular GeneticistDirector of the Genetics LaboratoryAl Jalila Children’sUnited Arab Emirates Dr. Abou Tayoun[/caption] 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.
Alcohol, Author Interviews, Genetic Research, Nature, University of Pennsylvania / 05.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48375" align="alignleft" width="160"]Henry R. Kranzler, MDProfessor of PsychiatryPerelman School of MedicineUniversity of Pennsylvania Dr. Kranzler[/caption] 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. 
Author Interviews, Diabetes, Genetic Research, JAMA, Mental Health Research, Schizophrenia / 03.04.2019

MedicalResearch.com Interview with: [caption id="attachment_48354" align="alignleft" width="99"]Prof Sabine Bahn MD PhD MRCPsych FRSBCambridge Centre for Neuropsychiatric Research Prof. Bahn[/caption] Prof Sabine Bahn MD PhD MRCPsych FRSB Cambridge Centre for Neuropsychiatric Research [caption id="attachment_48355" align="alignleft" width="99"]Jakub Tomasik, PhDDepartment of Chemical Engineering and Biotechnology Dr. Tomasik[/caption] 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. 
Author Interviews, Endocrinology, Genetic Research / 24.03.2019

MedicalResearch.com Interview with: [caption id="attachment_48099" align="alignleft" width="200"]Emily J. Gallagher, MDAssistant Professor of MedicineEndocrinology, Diabetes and Bone DiseaseIcahn School of Medicine at Mount Sinai  Dr. Gallagher[/caption] 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.
Author Interviews, Genetic Research, JAMA, Prostate Cancer / 24.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47572" align="alignleft" width="160"]Masaki Shiota MD, PhD Department of Urology, Graduate School of Medical Sciences Kyushu University Fukuoka , Japan Dr. Shiota[/caption] Masaki Shiota MD, PhD Department of Urology Graduate School of Medical Sciences Kyushu University Fukuoka , Japan MedicalResearch.com: What is the background for this study? What are the main findings? Response:  3β-hydroxysteroid dehydrogenase-1 encoded by HSD3B1 is a rate-limiting enzyme required for all pathways of dihydrotestosterone synthesis, as well as converts abiraterone into Δ4-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor. A mutation (1245A>C) in HSD3B1 is shown to be resistant to proteasomal degradation, causing substantial accumulation of this enzyme and gain-of-function. Although the HSD3B1 (1245C) allele can be acquired by mutation, germ-line single nucleotide polymorphism (SNP; rs1047303) is also known to exist. Then, in this study, we investigated the significance of missense polymorphism in HSD3B1 gene among men treated with primary ADT or abiraterone. The results showed men carrying variant allele showed higher risk of progression in primary androgen-deprivation therapy, but vulnerable to abiraterone treatment.
Author Interviews, Genetic Research, Smoking, Tobacco / 22.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47612" align="alignleft" width="150"]Dennis Drayna, PhD Chief of the Laboratory of Communication Disorders and the Section on Genetics of Communication Disorders National Institute on Deafness and Other Communication Disorders Part of the National Institutes of Health DR. Drayna[/caption] Dennis Drayna, PhD Chief of the Laboratory of Communication Disorders and the Section on Genetics of Communication Disorders National Institute on Deafness and Other Communication Disorders Part of the National Institutes of Health MedicalResearch.com: What is the background for this study? Response: In the United States, there are striking racial differences in the rate of menthol cigarette use.  Tobacco use is a major preventable source of morbidity and mortality in the population, and menthol cigarette use by African Americans represents an important issue for attempts to address minority health disparities. There have been many studies that have documented the role of inherited factors that contribute to smoking or tobacco use.  However, no studies have examined the role of genetic factors specifically in menthol tobacco use.  The preference for menthol cigarettes among African Americans has previously been attributed to cultural factors or industry advertising practices directed at this group. In our study, we asked whether genetic factors could explain why African-American smokers choose menthol cigarettes over non-menthol cigarettes. Our initial hypothesis was that variation in genes that encode the known menthol receptors was important in this difference, although we designed our study to look at all 21,000 protein-coding genes in the genome.
Author Interviews, Dermatology / 19.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47488" align="alignleft" width="199"]Cicatricial Alopecia Courtesy of Dr. Amy McMichael MD The Department of Dermatology Wake Forest Baptist Medical Center Winston-Salem, North Carolina  Cicatricial Alopecia
Courtesy of Dr. Amy McMichael MD
The Department of Dermatology
Wake Forest Baptist Medical Center
Winston-SalemNorth Carolina[/caption] Eli Sprecher MD PhD Professor and Chair, Division of Dermatology Deputy Director General for R&D and Innovation Tel Aviv Sourasky Medical Center Frederick Reiss Chair of Dermatology Sackler Faculty of Medicine Tel Aviv University, Tel Aviv, Israel and MedicalResearch.com: What is the background for this study? Response: Central centrifugal cicatricial alopecia (CCCA) is a form of hair loss (alopecia) which is extremely common and affects one in every 20 women of African origin. It starts usually during the fourth decade of life. Because it can be inherited from mothers to their children, it is thought to have a genetic basis. On the other hand, it is known to mainly affect women who use to groom their hair intensively. Thus it was thought that the disease stems from some form of inherited susceptibility to the damage incurred to the hair follicle by grooming habits. In the study we published, we searched for the genetic basis of CCCA. In contrast with the common form of alopecia (androgenetic alopecia or female pattern alopecia), CCCA is associated with scarring of the scalp skin, which means that once hair is lost, it will likely not re-grow.
Author Interviews, Personalized Medicine, Weight Research / 19.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47503" align="alignleft" width="130"]Ruth Loos, PhD The Charles Bronfman Professor in Personalized Medicine Director, Genetics of Obesity and Related Traits Program Co-Director, Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai New York, NY Dr. Loos[/caption] Ruth Loos, PhD The Charles Bronfman Professor in Personalized Medicine Director, Genetics of Obesity and Related Traits Program Co-Director, Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai New York, NY     MedicalResearch.com: What is the background for this study? Which type of body fat distribution carries greater risk of diabetes or other obesity-related health disorders? Response: Obesity broadly consists of two component; [1] there is overall body size (assessed using BMI) and [2] there is fat distribution (assessed using WHR). Both are “heritable”, which mean that they are in part determined by our genome (and the other part is determined by our lifestyle). Over the past 15 years, geneticists have used an approach to screen the whole genome of thousands of people to identify genetic variations that differ between e.g. obese people vs non-obese people. We have applied this approach to both components of obesity and have found so far that genes for “overall body size” seem to act in the brain, likely controlling hunger, satiety, reward, etc., whereas the genes that determine where in the body the excess fat will be stored when you gain weight (i.e. fat distribution) seem to act more “locally” at the fat cell level itself, determining the storage and release of fat. 
Aging, Author Interviews, Genetic Research / 12.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47448" align="alignleft" width="200"]Yurii Aulchenko Co-founder and Chief Scientist of PolyOmica Yurii Aulchenko[/caption] Yurii Aulchenko Co-founder and Chief Scientist of PolyOmica PolyOmica is a research & development company providing services and tools for quantitative genetics and functional genomics. [caption id="attachment_47449" align="alignleft" width="150"]Peter Fedichev Founder and Chief Science Officer of Gero Peter Fedichev[/caption] Peter Fedichev Founder and Chief Science Officer of Gero Gero is a data-driven longevity company developing innovative therapies that will strongly extend the healthy period of life also known as healthspan MedicalResearch.com: What is the background for this study? What are the main findings? Peter Fedichev, Gero: Age is the most important risk factor behind age-related diseases and death. Lifespan has increased quite dramatically over the last 150-200 years mostly due to the eradication of early-life mortality. What we find, however, is that the healthspan, understood as the chronic diseases-free period, is also on the rise, but not so much. It appears that lifespan is modifiable by interventions, at least in lab animals. It is therefore crucial to understand if the biology behind human healthspan. Is it the same as that of lifespan? What are the molecular pathways and genetic factors controlling the healthspan? At the end, we would like to develop interventions that extend not only lifespan, but also the healthspan. Everyone wants to stay healthy! Yurii Aulchenko, PolyOmica: We studied the incidence of the most prevalent age-related diseases in the large UK Biobank, one of the best repositories of biologically and medically relevant data from a very large cohort of aging individuals. We observed that the incidence (the chances of) all the major diseases increased exponentially with age. The diseases risk doubling time was about eight years, same as the mortality doubling time from the Gompertz mortality law, discovered as early as in 1825 and used in life insurance ever since. The similar patterns of age-dependent risk acceleration suggest a major common driver behind the diseases, that is most plausibly aging itself. Peter Fedichev, Gero: The incidence of the diseases could, therefore, be used as a biomarker of aging process. We used the age at the onset of the first age-related disease (the end of healthspan) as the target for a genome-wide association study (GWAS) and identified as many as 12 genetic loci associated with human healthspan.
Author Interviews, Genetic Research, JAMA, Race/Ethnic Diversity, Stroke / 11.02.2019

MedicalResearch.com Interview with: [caption id="attachment_47440" align="alignleft" width="133"]Dr. Marini Dr. Marini[/caption] Sandro Marini, MD Research Fellow Jonathan Rosand Laboratory Massachusetts General Hospital Boston, MA 02114 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The epsilon(ε) 4 allele of the Apolipoprotein E (APOE) gene increases risk for Alzheimer’s disease (AD) and intracerebral hemorrhage (ICH). In both diseases, it is believed to increase risk through the deposition of beta-amyloid within the brain and blood vessels, respectively. The effect of APOE ε4 on both AD and ICH risk changes across populations, for unclear reasons. In our study, we confirmed the role of APOE ε4 for ICH risk in whites and found that the risk-increasing effect of the 4 allele is demonstrable in Hispanics only when balancing out the effect of hypertension.