Author Interviews, Genetic Research, Pediatrics, Weight Research / 22.05.2018

MedicalResearch.com Interview with: “Great Grandmother” by David Amsler is licensed under CC BY 2.0Rebecca Somerville MB BCh BAO, BMedSci, MRCPI, MPH, PhD School of Public Health, Physiotherapy and Sports Science University College Dublin Dublin, Ireland  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Rates of obesity in the Western world have increased dramatically over recent decades. The negative health consequences of obesity are well known and significant amounts of research have been conducted into the causes and possible solutions. While it is clear that there have been massive changes in diet and physical activity at a societal level that are primarily responsible for this 'obesity epidemic', it is less clear the extent to which obesity, once established, or risk factors for same, can be perpetuated down generations. Family studies lend opportunity to explore these questions, however there are few world wide which incorporate 3 generations. We therefore sought to examine patterns of central adiposity, as measured by waist circumference, between grandparents and their grandchildren, separately in maternal and paternal lines. We were able to utilize prospectively collected data from the Lifeways Cross-Generation Cohort Study. This is a longitudinal birth cohort, established in Ireland in 2001, involving up to 7 members of the same family (mother, father, child and 4 grandparents). In the 589 families where a child had a waist circumference measurement we found that, at the age of both 5 and 9, there was a direct relationship between the waist circumference of the maternal grandmother and her grandchild (both male and female). This remained after adjustment for a wide range of confounding variables including mother's waist circumference. There was no relationship seen with any of the other grandparents. (more…)
Author Interviews, Exercise - Fitness, Genetic Research, Heart Disease / 19.05.2018

MedicalResearch.com Interview with: Prof. Patricia Munroe PhD Professor of Molecular Medicine William Harvey Research Institute Barts and The London School of Medicine and Dentistry Queen Mary University of London MedicalResearch.com: What is the background for this study? Response: Over the years, it has become increasingly evident that impaired capacity to increase heart rate during exercise and reduce heart rate following exercise are important predictors of all-cause and cardiovascular mortality. A person's capability to regulate their heart rate is the result of complex interactions of biological systems, including the autonomic nervous and hormonal systems. Prior work has demonstrated that genetic factors significantly contribute to variations in resting heart rate among different individuals, but less was known about the genetic factors modulating the response of heart rate to exercise and recovery. (more…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids, Vanderbilt / 18.05.2018

MedicalResearch.com Interview with: Wei-Qi Wei, MD, PhD Assistant Professor Department of Biomedical Informatics Vanderbilt University Nashville, TN 37203 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The study was motived by the clinical observation that some patients develop coronary heart disease events despite taking statins, one of our most effective drugs to reduce cardiovascular risk. We collected data within the eMERGE network of people taking statins and monitored them for development of coronary heart disease events over time.  We  conducted a genome-wide association study of those with events compared to those without events. Our results showed that single nucleotide polymorphisms (SNPs) on the LPA gene were associated with a significantly increased risk of coronary heart disease events. Individuals with the variant were 50% more likely to have an event. More importantly, even among patients who achieved ideal on-treatment LDL cholesterol levels (<70 mg/dL), the association remained statistically significant. We then did a phenome-wide association study to see if other diseases or conditions were associated with these LPAvariants. The major associated conditions were all cardiovascular. This sort of study can highlight potential other indications for a drug targeting this pathway and suggest potential adverse events that might be experienced from targeting this pathway. Clearly, more and larger studies will be needed to truly understand the potential risks and benefits of a future drug targeting this pathway.  (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 17.05.2018

MedicalResearch.com Interview with: Tobias Kaufmann PhD Norwegian Centre for Mental Disorders Research (NORMENT), KG Jebsen Centre for Psychosis Research, Division of Mental Health and Addiction, Oslo University Hospital & Institute of Clinical Medicine University of Oslo, Oslo, Norway MedicalResearch.com: What is the background for this study? What are the main findings? Response: Over the past years, a lot of work has pointed toward impaired brain networks in schizophrenia. With this work we assessed brain network stability across different loads of a cognitive task using functional magnetic resonance imaging of the brain. Based on our earlier work on adolescents with pre-clinical signs of mental illness who showed decreased stability of networks across different tasks and conditions, we hypothesized that brain networks in adults with schizophrenia show similar properties of decreased stability. Our results confirmed this hypothesis. Stability was reduced in several large-scale brain networks across the sampled age range from early adulthood to the sixties. Further, network stability was associated with polygenic risk for schizophrenia as well as cognitive task performance. (more…)
Author Interviews, Genetic Research, JAMA, UCSF / 12.05.2018

MedicalResearch.com Interview with: Allison W. Kurian, M.D., M.Sc. Associate Professor of Medicine (Oncology) and of Health Research and Policy Director, Women’s Clinical Cancer Genetics Program Stanford University School of Medicine Stanford, CA 94305-5405  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Changes in genetic sequencing technology and regulation have allowed much cheaper testing of many more genes in recent years. We investigated how these changes have affected hereditary cancer risk evaluation in women newly diagnosed with breast cancer. The main findings are that more comprehensive multiple-gene sequencing tests have rapidly replaced more limited tests of two genes (BRCA1 and BRCA2) only. This has helped patients by doubling the chance of finding an important gene mutation that can change their treatment options. However, there are important gaps in how this new, more comprehensive sequencing is used: more testing delays and more uncertain results, particularly among racial/ethnic minority women.  (more…)
Author Interviews, BMJ, Genetic Research, Pediatrics / 10.05.2018

MedicalResearch.com Interview with: “Newborn” by Brad Carroll is licensed under CC BY 2.0Dr Sian Taylor-Phillips MPhys, PhD Associate Professor Screening and Test Evaluation / NIHR Career Development Fellow Division of Health Sciences Warwick Medical School University of Warwick Coventry MedicalResearch.com: What is the background for this study? What are the main findings? Response: In newborn blood spot screening a small amount of blood is taken from newborn babies heels, and this is tested for a range of rare diseases. The idea is to detect each disease earlier when it is more treatable. However, it would be better not to test for some diseases, for example if the test is inaccurate so worries parents that their baby may have a serious illness when they do not. Some countries test for as few as 5 diseases and others as many as 50. In this study we investigated how different countries choose which diseases to test for. We found that many national recommendations on whether to screen newborn babies for rare diseases do not assess the evidence on the key benefits and harms of screening. Evidence about the accuracy of the test was not considered in 42% of recommendations, evidence about whether early detection at screening has health benefits was not consulted in 30% of recommendations, and evidence around the potential harm of overdiagnosis where babies have variants of the disease that would never have caused any symptoms or ill effects was not considered in 76% of recommendations. We also found through meta-analysis that when a systematic review was used to bring together the evidence then countries were less likely to recommend screening for the disease. (more…)
Author Interviews, Genetic Research, Weight Research / 09.05.2018

MedicalResearch.com Interview with: “Mmm...hamburgers” by jeffreyw is licensed under CC BY 2.0Dr. Peter Kühnen Institute for Experimental Pediatric Endocrinology Charité Universitätsmedizin Berlin Berlin Germany  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: We are focusing our interest on rare monogenic forms of obesity. The hormones leptin and MSH are playing a pivotal role for the regulation of satiety and body weight. Mutations within this pathway, e.g. in the leptin receptor gene, are leading to severe hyperphagia and early onset obesity.  Although tremendous effort it is extremely difficult for the affected patients to stabilize their body weight for a longer period of time. For this reason it has been analyzed within this investigated initiated trial whether patients with a leptin receptor mutation benefit from a treatment with the MC4R agonist setmelanotide. The treatment led to a reduction of the initially increased hunger feeling and to a reduction of body weight. Additionally, we identified molecular evidences that a specific signaling cascade of the MSH receptor (MC4R) is of importance for the regulation of body weight. (more…)
AACR, Author Interviews, Genetic Research / 18.04.2018

MedicalResearch.com Interview with: Ed Liu, M.D President and CEO The Jackson Laboratory (JAX) MedicalResearch.com: What is the background for this study? What are the main findings? Response: A few years ago we and others identified a complex genomic instability profile commonly found in the genomes of breast, ovarian and endometrial carcinomas, which is characterized by hundreds of isolated head-to-tail duplications of DNA segments, called tandem duplications. We refer to this configuration as the tandem duplicator phenotype, or TDP. In this study, we perform a meta-analysis of over 2,700 cancer genomes from over 30 different tumor types and provide a detailed description of six different types of TDP, distinguished by the presence of tandem duplications of different sizes. Collectively, these profiles are found in ~50% of breast, ovarian and endometrial carcinomas as well as 10-30% of adrenocortical, esophageal, stomach and lung adeno-carcinomas. We show that distinct genetic abnormalities associate with the distinct TDPs, clearly suggesting that distinct molecular mechanisms are driving TDP formation. In particular, we provide strong evidence of a casual relationship between joint abrogation of the BRCA1 and TP53 tumor suppressor genes and the emergence of a short-span (~11 Kb) TDP profile. We also observe a significant association between hyper-activation of the CCNE1 pathway and TDP with medium-span (~230 Kb) tandem duplications, and between mutation of the CDK12 gene and medium- and large-span TDP (coexisting 230 Kb and 1.7 Kb tandem duplications). Importantly, we find that different forms of TDP result in the perturbation of alternative sets of cancer genes, with short-span TDP profiles leading to the loss of tumor suppressor genes via double transections, and larger-span TDP profiles resulting in the duplication (i.e. copy number gain) of oncogenes and gene regulatory elements, such as super-enhancers and disease-associated SNPs.  (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA / 06.04.2018

MedicalResearch.com Interview with: Stella Aslibekyan, PhD Associate Professor PhD Program Director Department of Epidemiology University of Alabama at Birmingham MedicalResearch.com: What is the background for this study? What are the main findings? Response: When the human genome was sequenced in 2003, there were somewhat unrestrained expectations of unraveling all etiologic mysteries and discovering breakthrough treatments. Needless to say, that did not happen, in part because individual genetic variants can only account for a small fraction of trait variability. Since then, epigenetics-- the study of mitotically heritable changes in gene expression-- has emerged as another promising avenue for understanding disease risk. The best studied epigenetic process in humans is DNA methylation, and earlier studies (including some from our group) have shown interesting associations between changes in methylation in specific genomic regions and cardiovascular disease traits, e.g. plasma cholesterol levels. In this project, we have combined DNA methylation data on thousands of individuals from multiple international cohorts and interrogated epigenetic contributions to circulating tumor necrosis factor alpha (TNFa), a marker of systemic inflammation. We identified and replicated several epigenomic markers of TNFa, linked them to variation in gene expression, and showed that these methylation changes (which were located in interferon pathway genes) were predictive of coronary heart disease later in life. Interestingly, the variants we discovered were not sequence-dependent (in other words, they were not associated with any genetic mutations), highlighting the role of the environment. (more…)
Author Interviews, Genetic Research, Ophthalmology / 05.04.2018

MedicalResearch.com Interview with: Wen-Tao Deng, Ph.D. Department of Ophthalmology, College of Medicine| University of Florida, Gainesville, FL MedicalResearch.com: What is the background for this study? What are the main findings? Response: Blue cone monochromay (BCM) is a devastating vision disorder characterized by loss function of both L- and M-cones due to mutations in the L- and M-opin gene cluster on the X chromosome. BCM patients display severely reduced visual acuity, loss of color-vision, myopia, nystagmus, and minimally detectable cone-mediated electroretinogram. In our studies, we showed that an M-opsin knockout mouse model resembles human BCM, and expression of either human M- or L-opsin individually or combined through adeno-associated viral vector promotes regrowth of cone outer segments and rescues M-cone function in the treated M-opsin dorsal retin (more…)
Author Interviews, Colon Cancer, Genetic Research, JAMA / 03.04.2018

MedicalResearch.com Interview with: Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH  4322 MedicalResearch.com:  What is the background for this study?  What are the main findings? Response: The background is that we had recently shown that some colorectal cancer patients who underwent traditional screening for Lynch syndrome were eventually found to have double somatic (two acquired) mutations in the MMR genes and they did not have Lynch syndrome at all. This was discovered after their tumor had already had MSI and/or IHC screening test, followed by MLH1 methylation and/or BRAF testing, followed by germline DNA testing on a blood sample from the patient for MMR gene mutations, then finally by sequencing their tumor. This gave us the idea to reverse the sequence and start with tumor sequencing since it might streamline testing, save time, and prevent several other tests. In addition, we knew that all stage IV colorectal cancer are already supposed to have tumor sequencing of the KRAS, NRAS, and BRAF genes and MSI testing for treatment purposes. Our hypothesis was that an upfront tumor sequencing test could replace all these separate tests with similar sensitivity and specificity. (more…)
Author Interviews, Genetic Research, Nature, OBGYNE, UCLA / 22.03.2018

MedicalResearch.com Interview with: Marlena Fejzo, PhD Aassociate researche David Geffen School of Medicine UCLA.  MedicalResearch.com: What is the background for this study? Response: Most women experience some nausea and vomiting of pregnancy, and the worst 2% are diagnosed with Hyperemesis Gravidarum which is associated with poor maternal and fetal outcomes. I had HG in 2 pregnancies. In my second pregnancy my HG was so severe that I could not move without vomiting and did not keep any food or water down for 10 weeks. I was put on a feeding tube, but ultimately lost the baby in the second trimester. I am a medical scientist by training so I looked into what was known about HG. At the time, very little was known, so I decided to study it. I partnered with the Hyperemesis Education and Research Foundation (HER) and we did a survey on family history of .Hyperemesis Gravidarum that provided evidence to support a role for genes. I collected saliva samples from HG patients and their unaffected acquaintances to do a DNA study. Then I partnered with the personal genetics company, 23andMe to do a genome scan and validation study, which identified 2 genes, GDF15 and IGFBP7, linked to HG. (more…)
Author Interviews, Biomarkers, Breast Cancer, Cancer Research, Genetic Research / 26.02.2018

MedicalResearch.com Interview with: Maureen E. Murphy, Ph.D. Program Leader and Professor Molecular and Cellular Oncogenesis and Subhasree Basu PhD Postdoctoral researcher The Wistar Institute Philadelphia, PA 19104 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Unlike most other genes that are intimately involved in the cause of cancer, the p53 gene displays considerable genetic variation; in other words, p53 is unusual among cancer genes in that the amino acids in p53 protein can frequently differ amongst different populations and ethnic groups. Additionally, unlike most other tumor suppressor genes, when p53 is mutated in a tumor, as it is in 50% of human cancers, that mutant protein now has a positive function in cancer progression, changing tumor metabolism and promoting tumor metastasis. In this study, the authors analyze for the first time the impact of a common genetic variant in p53 (single nucleotide polymorphism, or SNP) in the ability of mutant p53 to promote tumor metabolism and metastasis, and they find significant differences.  (more…)
Author Interviews, Breast Cancer, Genetic Research / 19.02.2018

MedicalResearch.com Interview with: Amanda Toland, PhD, Cancer biology and genetics researcher of The Ohio State University Comprehensive Cancer Center -- Arthur G. James Cancer Hospital and Richard J. Solove Research Institute MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Breast Information Core (or BIC) is a database that catalogs BRCA1 and BRCA2 sequenced variants.  The BIC is hosted by the National Human Genome Research Institute at NIH and has a steering committee that oversees the BIC and has members from Europe, the middle East, Australia and the US.  In BIC SC discussions, we learned that there are differences in how BRCA1/2 clinical is testing between countries. To characterize this variation, we performed an international survey of 86 genetic testing labs from around the world. Our main findings are that there were many variations between testing laboratories.  These include: technologies differed for finding “large” genetic sequence variants, what parts of the genes were assessed, how genetic variants were classified as disease associated or not being associated with diseases, if genetic sequencing information was shared in public databases and testing volume. (more…)
Author Interviews, Dengue, Genetic Research, PLoS / 16.02.2018

MedicalResearch.com Interview with: Luisa Pereira PhD Institute for Research and Innovation in Health University of Porto  MedicalResearch.com: What is the background for this study? What are the main findings? Response: By using admixture mapping along the genome in Thai cohorts, we were able to identify new candidate genes conferring protection/susceptibility to dengue fever. A very interesting result was that the set of genes differed with the dengue phenotype: genes coding proteins that may link to the virus, conditioning its entrance in the host cells and mobility therein were associated with the less severe phenotype; genes related with blood vessels permeability were associated with the dengue shock syndrome.  (more…)
Author Interviews, Genetic Research, OBGYNE / 08.02.2018

“Pregnancy 1” by operalynn is licensed under CC BY 2.0MedicalResearch.com Interview with: Professor Jane Halliday, PhD Group Leader, Public Health Genetics Genetics Murdoch Childrens Research Institute The Royal Children’s Hospital Parkville, Victoria  AUS  MedicalResearch.com: What is the background for this study? Response: The aim of the study was to examine the choice that pregnant women make about the amount of genetic information they want from their pregnancy. Women who underwent prenatal testing via chorionic villus sampling (CVS) or amniocentesis were recruited from across seven sites in Victoria. Provision of this choice is not routinely offered but we thought it was important to look at this issue carefully, in a real-time setting, because, over the last five years, advances in technology have transformed how genetic abnormalities can be detected during a pregnancy.  Rather than examining genetic material (chromosomes) down the microscope, it is now possible to use a technique called ‘microarray’ which can do the analysis with 100 times greater depth than can be achieved using a microscope. The plus side is that the microarray technique can detect a far greater number of potentially important genetic differences; but a down side is that it can also detect many changes for which the impact on the health of the baby is unknown or uncertain. Examples of genetic differences that carry certainty are major chromosome abnormalities such as the trisomies e.g. Down Syndrome, and deletions associated with severe intellectual disability in 100% of cases, e.g. 1p.36 deletion. Uncertain findings are the various small deletions and duplications that are known to only have an adverse outcome in 10-20% of people with them. All participants were provided with a decision aid which described in detail the choice available in regards to the genetic information. The options were ‘targeted’, where only the information that would affect health of the baby was provided, or ‘extended’, where all information, even the uncertain aspects, was provided. Participants were asked to read the decision aid, complete a ten minute survey along with indicating their choice of genetic information. (more…)
Author Interviews, Biomarkers, BMJ, Genetic Research, Prostate Cancer, UCSD / 29.01.2018

MedicalResearch.com Interview with: “DNA” by Caroline Davis2010 is licensed under CC BY 2.0Tyler Seibert, MD, PhD Radiation Oncology Center for Multimodal Imaging & Genetics UC San Diego MedicalResearch.com: What is the background for this study? Response: Prostate cancer is an extremely common condition in men. Many die from it each year, and many others live with debilitating pain caused by prostate cancer. Screening for prostate cancer with prostate-specific antigen (PSA) testing can be effective, but there are concerns with the test.
  • First, screening everyone gives a large proportion of false-positive results, and those men end up undergoing unnecessary procedures such as prostate biopsy. S
  • econd, a significant portion of men who develop prostate cancer will develop a slow-growing form of the disease that is likely not life-threatening and may not require treatment. These concerns have led to a drop in prostate cancer screening. But avoiding screening leaves a large number of men vulnerable to diagnosis of an aggressive prostate cancer at a later stage, when it is more difficult—or impossible—to be cured. Doctors are left to guess which of their patients are at risk of aggressive disease and at which age they need to start screening those patients.
Our study sought to develop a tool to provide men and their doctors with objective, personalized information about each man’s risk of prostate cancer. Based on the man’s genetics, we wanted to predict the risk of aggressive prostate cancer and at what age in his life that risk becomes elevated. (more…)
Author Interviews, Education, Genetic Research / 26.01.2018

“Reading is fun!” by Isaac Wedin is licensed under CC BY 2.0MedicalResearch.com Interview with: Bruno Sauce, PhD and Louis D. Matzel, PhD Department of Psychology, Program in Behavioral and Systems Neuroscience Rutgers University New Jersey, USA  MedicalResearch.com: What is the background for this study? Response: Scientists have known for decades that intelligence has a high heritability, which means that much of the individual differences in IQ we see in people are due to genetic differences. Heritability is a value that ranges from 0.0 (meaning no genetic component) to 1.0 (meaning that the trait is completely heritable). For example, the heritability of breast cancer is estimated at 0.27; the heritability of body mass index is 0.59; and the heritability of major depression is 0.40. In comparison, the heritability of IQ is estimated to be as high as 0.8 – quite a high value! More recently, however, there have been studies showing that intelligence has a high malleability: the studies cover cognitive gains consequent to adoption/immigration, changes in IQ’s heritability across life span and socioeconomic status, gains in IQ over time from societal and scientific progress, the slowdown of age-related cognitive decline, the gains in intelligence from early education, differences in average IQ between countries due to wealth and development, and gains in intelligence that seem to happen from working memory training. Intelligence being both highly heritable and highly malleable is seemingly paradoxical, and this paradox has been the source of continuous controversy among scientists. Why does it matter? Because IQ predicts many important outcomes in life, such as academic grades, income, social mobility, happiness, marital stability and satisfaction, general health, longevity, reduced risk of accidents, and reduced risk of drug addiction (among many other outcomes). A clear understanding of the genetic and environmental causes of variation in intelligence is critical for future research, and its potential implications (and applications) for society are immense. (more…)
Author Interviews, Cognitive Issues, Genetic Research, JAMA, Medical Imaging, Mental Health Research / 25.01.2018

MedicalResearch.com Interview with: “The Fourth Sex: Adolescent Extremes” by Victor Soto is licensed under CC BY 2.0Dag Alnaes, PhD Norwegian Centre for Mental Disorders Research KG Jebsen Centre for Psychosis Research Division of Mental Health and Addiction, Oslo University Hospital Oslo, Norway  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The transition from childhood to adulthood is characterized by swift and dramatic changes, both in our environment and in our brains. This period of life also coincides with the onset of many mental disorders. To gain a better understanding of why, the clinical neurosciences must attempt to disentangle the complex and dynamic interactions between genes and the environment and how they shape our brains. The ultimate goal is to be able to predict which individuals are at risk before clinical symptoms appear. Advanced brain imaging has been proposed to represent one promising approach for such early detection, but there is currently no robust imaging marker that allows us to identify individuals at risk with any clinically relevant degree of certainty. Our study shows that self-reported early signs of mental illness are associated with specific patterns of brain fiber pathways in young people, even if they may not fulfill criteria for a formal diagnosis or are currently in need of treatment.  (more…)
Author Interviews, Genetic Research, Neurology / 25.01.2018

MedicalResearch.com Interview with: Ona Bloom PhD “Duluth Boat Show - Sea Lamprey Booth” by USFWSmidwest is licensed under CC BY 2.0Associate Professor, Center for Autoimmune, Musculoskeletal and Hematopoietic Diseases, The Feinstein Institute for Medical Research Associate Professor, Department of Molecular Medicine, Donald and Barbara Zucker School of Medicine at Hofstra/Northwell MedicalResearch.com: What is the background for this study? What are the main findings? Response: Scientists have known for years that an ancient species of fish called the lamprey has a remarkable ability to rebuild their spinal cord after it’s been severed. After the lamprey spinal cord is cut, they recover from paralysis to fully swimming again in about twelve weeks, without taking any medicines or other treatments. We are studying the lamprey because we want to know the recipe of molecular ingredients that supports successful recovery after spinal cord injury. The genome of this animal was reported about 5 years ago, in a publication led by my colleagues Dr. Jeramiah Smith at the University of Kentucky and Dr. Weiming Li at Michigan State University.  It turns out that many aspects of the lamprey genome are similar to ours, particularly in the central nervous system. Therefore, we think it is a reasonable expectation that what we learn from lamprey could give us some relevant clues about what might be different about the responses in mammals and other animals that are not good at regenerating their spinal cord. In this study, we found that the expression of many genes in the spinal cord and brain of lampreys change during their recovery from spinal cord injury. Some of the genes that get activated are similar to what happens when our peripheral nervous system is injured, which is better at regenerating than the central nervous system. We also identified that a pathway called the Wnt pathway plays an important role in the regeneration and recovery process. This is a large, complex network of genes that are important in many biological processes, from embryological development in fruit flies to cancer in humans. (more…)
Author Interviews, Genetic Research, JAMA, Neurology, Parkinson's / 25.01.2018

MedicalResearch.com Interview with: Rachel Saunders-Pullman, MD, MPH Associate Professor of Neurology Icahn School of Medicine at Mount Sinai Chief, Movement Disorders, Mount Sinai Beth Israel Co-Director Clinical/Translational Research and Research Mentoring Movement Disorders, Department of Neurology, Mount Sinai Beth Israel New York, NY 10003 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: There is a diversity in causes of Parkinson’s Disease (PD), and this may lead to heterogeneity in drug response. While LRRK2 PD due to G2019S mutations may fully mimic idiopathic PD (IPD), cross-sectional study suggests that the course may be slightly milder than IPD. Further, the pathology is heterogeneous with a minority not demonstrating Lewy bodies, and this may also correspond to less severe non-motor features. To better understand the course of PD associated with the G2019S LRRK2 mutation (the most common LRRK2 mutation), we evaluated motor and cognitive progression in individuals enrolled in the LRRK2 Ashkenazi Jewish Consortium. Subjects were recruited from a Center in Tel Aviv, Israel, Sourasky Medical Center, and from two centers in New York, Columbia University and Mount Sinai Beth Israel. 144 participants were LRRK2 mutation carriers and 401 were not. We utilized all study visits, and constructed linear mixed-effects models to estimate the association between harboring the LRRK2 mutation and rate of change of both motor features- as assessed by the Unified Parkinson’s Disease Rating Scale (UPDRS), and cognition, as measured by the Montreal Cognitive Assessment Scale (MoCA). Models adjusted for sex, site, age, disease duration and (for the motor models) cognitive score. We found a small but significant difference in rate of progression, with LRRK2 PD progressing at 0.69 points/year, and IPD at 1.06 points/year. While the cognitive decline was also less in the LRRK2 PD (-0.10 vs. -0.19 in the IPD, this difference was not statistically different (p=0.08). (more…)
Author Interviews, Emory, Genetic Research, JAMA, Ophthalmology / 24.01.2018

MedicalResearch.com Interview with: Eldon E. Geisert, PhD Professor of Ophthalmology Emory School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: In the late 1990s a group of doctors began a study of glaucoma patients to determine if there were phenotypes that are predictive for developing glaucoma. In this Ocular Hypertension Treatment Study (OHTS) one of the highly correlated ocular traits was central corneal thickness (CCT). The early clinical studies found that people with thinner corneas were at a higher risk of developing glaucoma. In two large studies, examining thousands of people a number of genes were identified that were risk factors for glaucoma or that controlled CCT in humans. In both cases the identified genes accounted for less than 10% of the genetic risk for glaucoma and less than for 10% of the genetic control for CCT. There was little data linking the genetic control of CCT to the glaucoma risk. Our group has taken an indirect approach to the question, using well-defined mouse genetic system to identify genes modulating CCT and then interrogating human glaucoma data to determine if these genes are associated with glaucoma risk.   (more…)
Author Interviews, FDA, Genetic Research, Ophthalmology / 15.01.2018

MedicalResearch.com Interview with: Dr. Stephen Rose PhD Chief Research Officer Foundation Fighting Blindness (FFB) Dr. Rose comments on the announcement of the FDA approval of voretigene neparvovec (LUXTURNA™) gene therapy for inherited blindness due to mutations in the RPE65 gene. What is the background for this announcement? What were the main findings from the study? Response: While it has been 30 years since the RPE65 gene was identified as causing Leber’s Congenital Amaurosis, this shows that it is possible to have an effective gene therapy for an inherited disease. As the first gene therapy for the eye or for an inherited disease, LUXTURNA is a historic milestone in the search for cures for all inherited retinal diseases (IRDs). As a one-time gene therapy, LUXTURNA will not only be life-changing for patients with vision loss due to mutations in the RPE65 gene, it also provides critical momentum for gene therapies - for the eye and other diseases - now in the clinic.  (more…)
Annals Internal Medicine, Author Interviews, Diabetes, Genetic Research, University of Pittsburgh / 07.01.2018

MedicalResearch.com Interview with: Xiangwei Xiao, M.D., Ph.D. Assistant Professor of Department of Surgery, Children’s Hospital of Pittsburgh University of Pittsburgh School of Medicine, Pittsburgh, PA MedicalResearch.com: What is the background for this study? Response: Diabetes is a prevalent chronic disease characterized by persistently high blood glucose. Diabetes has two main subtypes, type 1 diabetes and type 2 diabetes. In type 1 diabetes, the immune system attacks and destroys insulin-producing beta cells in the pancreas, resulting in high blood levels of glucose. In type 2 diabetes, the beta cells do not produce enough insulin or the body is not able to use insulin effectively. (more…)
Author Interviews, Genetic Research, Pharmaceutical Companies / 17.12.2017

MedicalResearch.com Interview with: Alexander S Hauser, PhD student MRC Laboratory of Molecular Biology Cambridge UK Department of Drug Design and Pharmacology, University of Copenhagen Copenhagen, Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: The prevalence and impact of genetic variation among all human G protein coupled receptors (GPCRs) that are targeted by FDA-approved drugs remain unknown. In this study, we present a comprehensive analysis and map of the pharmacogenomics landscape of GPCR drug targets. The key highlights are: - GPCRs targeted by drugs show extensive genetic variation in the human population - Variation occurs in functional sites and may result in altered drug response - Understanding GPCR genetic variation may help reduce global healthcare expenses (more…)
Author Interviews, Brigham & Women's - Harvard, Cancer Research, Genetic Research, JAMA / 15.12.2017

MedicalResearch.com Interview with: Annette S. Kim, MD, PhD Associate Professor, Harvard Medical School Brigham & Women's Hospital Boston MA 02115  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The recent debate on laboratory developed tests (LDTs) and FDA-approved companion diagnostics (FDA-CDs) has centered upon both the regulatory and performance aspects of LDTs and we, at the College of American Pathologists (CAP), had the data through our proficiency testing (PT) programs to address the latter point, performance that we wanted to share with the community.  We analyzed almost 7000 PT responses on three molecular oncology tests, those for BRAF, EGFR, and KRAS mutations, and found that both LDTs and FDA-CDs demonstrated excellent performance, with both test types exceeding 97% accuracy overall. The second key finding of the study was that more than 60% of all laboratories in our study that were using an FDA-CD kit report using it with modifications from the FDA-approved protocol.  These modifications in fact render these test LDTs.  These modifications appear to be driven by the exigencies of real day-to-day clinical practice that requires adapting the assays to meet the needs of a variety of clinical situations that may not be accommodated by the FDA-approved protocol.  These modifications include, for example, the testing of other tumor types that may carry targetable variants, different types of input specimen preparations available in pathology such as cytology smears or other fresh specimens rather than paraffin blocks, and availability of different methods of DNA quantification that those mandated by the FDA approval based upon pre-existing technologies in the laboratories.  In the clinical laboratory, we are always acutely aware that there is a patient awaiting this result. Therefore, we validate our assays to ensure that we can provide reliable and accurate results from our laboratory under as many varied clinical situations as possible. These data support that practice. (more…)
Author Interviews, Genetic Research, Melanoma / 14.12.2017

MedicalResearch.com Interview with: Hildur Helgadottir, M.D., Ph.D. Department of Oncology Karolinska University Hospital MedicalResearch.com: What is the background for this study? What are the main findings? Response: Malignant melanoma of the skin is one of the fastest increasing cancer types in the West. The main risk factors for melanoma are UV light exposure and hereditary factors. It is therefore relatively common for the afflicted to have family members with the disease. Inherited mutations of the tumour suppressor gene CDKN2A are the strongest known risk factors for familial melanoma and mutations in this gene also increase the risk of other cancers. Children, siblings or parents of mutation carriers have a 50-50 chance of also having the mutation, which can be identified with a gene test. The present study included Swedish and American families with inherited CDKN2A mutations. The researchers studied whether family members who have not inherited the mutation have any higher than normal risk of developing melanoma or other cancers. Melanoma, but no other cancers, was more common in the non-carriers in these families compared to the normal population. The phenomenon whereby non-carriers of a specific mutation copy the phenotype (in this case melanoma) from their mutation-carrying relatives is known as phenocopy. Phenocopy can be caused by other risk-modifying genes or exposure patterns that increase the probability of the specific phenotype manifesting itself. Previous studies have shown that people with the mutation who also have certain pigmentation variants run an even higher risk of melanoma. Even though the CDKN2A mutation should be present in all populations, it has almost exclusively been identified in families with a Caucasian heritage.This suggests that dark-skinned people with this mutation probably don’t develop melanoma as often and are therefore not tested for this specific mutation, presumably because they lack the risk-modifying pigmentation variants that increase the risk of melanoma. The researchers believe that such pigmentation variants also contribute to a higher melanoma risk in the family members who do not carry the mutation. (more…)
Author Interviews, Genetic Research, Weight Research / 08.12.2017

MedicalResearch.com Interview with: David Meyre PhD Associate Professor, McMaster University, Dept. of Health Research Methods, Evidence, and Impact Hamilton, Ontario Canada Visiting Professor, University of Lorraine, Inserm Nutrition-Genetics-Environmental Risks MedicalResearch.com: What is the background for this study? What are the main findings? Response: While the average body mass index has reached a plateau in Western countries such as the United States, extreme forms of obesity are still on the rise. The origins of super obesity are still poorly understood. We studied the effects of 37 well-established obesity genes on body-mass index in 75,230 adults with European ancestry using innovative statistical methods (conditional quantile regression and meta-regression models). We found that nine of the 37 genes (24%) make individuals gain more weight if they already have a high body mass index. The effect of these genes is amplified by four times, if we compare the 10% of the population at the low end of the body mass index, compared to the 10% at the high end. The plausible explanation is that there are interactions between these snowball obesity genes and risk environmental factors. (more…)
Author Interviews, Genetic Research, Weight Research / 05.12.2017

MedicalResearch.com Interview with: “Scale model” by brett jordan is licensed under CC BY 2.0William Barrington, PhD lead author on the study Recently graduated PhD student from the Threadgill lab David Threadgill, PhD Texas A&M College of Medicine and College of Veterinary Medicine & Biomedical Sciences, senior author MedicalResearch.com: What is the background for this study? What are the main findings? Response: Obesity and diet-induced diseases, such as cardiovascular disease, have reached epidemic proportions. The United States has offered universal dietary recommendations for decades, but they have been largely unsuccessful in reducing diet-induced diseases. These recommendations are largely built upon population-level data, which examines a large number of individuals and determines the average response to a dietary intervention. However, if there is large variation in responses within a population, then population-level data may be inadequate to improve health across genetically diverse individuals. Our study used four genetically diverse types of mice to examine how one’s genetics interact with diet to influence obesity and risk factors for cardiometabolic disease. The study compared four popular human diets (American, Mediterranean, Japanese, and Maasai/ketogenic). While all mice suffered detrimental effects from the American diet, the severity of disease varied widely across the types of mice. In comparison, no single diet improved health across all strains, but there was one or more diets that improved health in each strain. (more…)
Author Interviews, Dermatology, Genetic Research / 04.12.2017

MedicalReseaerch.com Interview with: Alicia R. Martin PhD, Postdoc Department of Genetics Stanford University Department of Medicine, Massachusetts General Hospital and Harvard Medical School Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA and Brenna M. Henn, Phd, Assistant Professor Department of Ecology and Evolution SUNY Stony Brook, NY  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Skin pigmentation varies more in Africa than in any other continent, and yet genetic studies of this and other traits are massively underrepresented there. Previous Eurasian study biases have instead focused on populations that vary less and have fewer variants contributing to baseline skin color. In our study, we compiled quantitative skin color measurements from a large, globally diverse set of individuals and populations to show that pigmentation varies more closer to the equator than in high latitude populations. We focused on the ‡Khomani San and Nama populations from South Africa, which diverged early along the modern human lineage from other populations and have lighter skin than equatorial Africans. We showed that skin pigmentation is roughly 100% heritable, but that previously identified genes make up a tiny fraction (~10%) of the variation present in these populations. We identified both known and new genes contributing to this variability. (more…)