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…)
Author Interviews, Genetic Research, Heart Disease, JAMA, Lipids / 15.11.2017

MedicalResearch.com Interview with: Hao Yu Chen, MSc Department of Medicine McGill University Montreal, Quebec, Canada Senior author: George Thanassoulis, MD, MSc MedicalResearch.com: What is the background for this study? Response: Aortic stenosis, a narrowing of the main valve of the heart, is the most common type of valve disease in the US. Present in more than 2.5 million individuals in North America, aortic stenosis can lead to heart failure and death. However, there is little known about the causes of aortic stenosis and how it should be treated. Previously, we have demonstrated that variants of the gene LPA are associated with the development of aortic stenosis. A better understanding of how this region contributes to aortic stenosis could identify higher-risk individuals and inform the development of new medical therapies for aortic stenosis.  (more…)
Author Interviews, Autism, Genetic Research, Nature / 12.11.2017

MedicalResearch.com Interview with: Woo-Yang Kim, Ph.D Associate Professor Department of Developmental Neuroscience Munroe-Meyer Institute University of Nebraska Medical Center Omaha, NE 68198-5960 MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions. Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown. Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes. Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability. (more…)
Abuse and Neglect, Author Interviews, Genetic Research, OBGYNE, Pediatrics / 10.11.2017

MedicalResearch.com Interview with: Professor Sir Nicholas Wald FRCP FRS Professor of Preventive Medicine Wolfson Institute of Preventive Medicine 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: Prenatal screening for Down’s syndrome (trisomy 21), Edwards syndrome (trisomy 18) and Patau syndrome (trisomy 13) by maternal plasma DNA analysis has an improved screening performance compared with conventional screening but is too expensive to be performed routinely and has a technical failure rate. The aim of the study was to take advantage of the improved screening performance of the DNA analysis in conjunction with the existing methods thereby providing a seamless testing interface between the “old” and the “new” methods that would detect a larger proportion of affected pregnancies with a much lower false-positive rate, at a much reduced cost compared with universal DNA testing and with no failed tests. The novel approach was to conduct a conventional screening test using a screening cut-off level that identifies about 10% of women with the highest risks of having an affected pregnancy (much higher than in conventional screening) and then to perform a DNA test using a portion of the original blood sample collected for the conventional test. Progressing to the DNA test was automatic for these high risk women without their having to be recalled for counseling and a fresh blood sample (ie as a reflex response hence the term “reflex DNA screening”). (more…)
Author Interviews, Genetic Research, Ophthalmology / 07.11.2017

MedicalResearch.com Interview with: Dr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting BlindnessDr. Stephen M. Rose, PhD Chief Research Officer Foundation Fighting Blindness Dr. Rose discusses the FDA advisory panel unanimously recommended approval of Spark Therapeutics' Gene Therapy Luxturna  for the treatment of patients with vision loss due to confirmed biallelic RPE65-mediated inherited retinal dystrophies, a group of rare blinding conditions caused by one of more than 220 different genes. MedicalResearch.com: Would you tell us a little about IRD? Whom does it affect and how?  How common is this disorder? Response: The retina at the back of the eye is responsible for collecting light and turning it into signals that are transmitted to the brain and interpreted as vision. Think of the retina as the film in a camera, or more recently the sensor at the back of a digital camera. Inherited rare retinal degenerations are when the retina at the back of the eye deteriorates and loses its ability to capture light, thereby leading to blindness. iRDs can affect anyone, no matter race or ethnicity. These are inherited conditions that are passed down from parents to children, if a parent or both parents are either affected already or are carriers for a variant in any of the over 250 genes responsible for retinal degeneration. There are over 15 different types of iRDs, with retinitis pigmentosa being the most common with a US affected population around 100,000. The rest of the iRDs make up another approximately 100,000 affected individuals in the US, so there are about 200,000 total affected individuals in the US. Worldwide these iRDs affect somewhere around one to two million individuals. (more…)
Alzheimer's - Dementia, Author Interviews, Cognitive Issues, Genetic Research, Nature / 07.11.2017

MedicalResearch.com Interview with: Dr Miguel Chillon PhD Department of Biochemistry and Molecular Biology Universitat Autonoma Barcelona Spain MedicalResearch.com: What is the background for this study? What are the main findings? Response: Klotho is a protein with an anti-aging and neuroprotective role. Recent studies show it prevents the development of cognitive problems associated with aging and Alzheimer's disease. Klotho works mainly by inhibiting the insulin / IGF-1 signaling pathway and decreasing the damage caused by oxidative stress in the brain. One of the latest results revealed that the concentration of Klotho in cerebrospinal fluid is significantly lower in Alzheimer's patients than in human controls of the same age; and it is lower in the elderly with respect to young adults. Our study used a gene therapy strategy to introduce the Klotho gene into the Central Nervous System of adult animals. With just a single injection of the Klotho gene, young adult animals were protected over time from the cognitive decline associated with aging in old animals. These exciting results pave the way to further advances in research and the development of a neuroprotective therapy based on Klotho. (more…)
Author Interviews, Dental Research, Genetic Research / 07.11.2017

MedicalResearch.com Interview with: “Dental Mold_002” by Ano Lobb is licensed under CC BY 2.0Alexandre R. Vieira, DDS. MS, PhD Professor, Director of Clinical Research,  Director of Student Research Department of Oral Biology Center for Craniofacial and Dental Genetics Department of Pediatric Dentistry School of Dental Medicine Department of Human Genetics Graduate School of Public Health Clinical and Translational Sciences Institute University of Pittsburgh  MedicalResearch.com: What is the background for this study? What are the main findings? Response: One aspect is the dilemma between continuing to use dental amalgams and the perception that composite resins are not as durable. We show that composite resin restorations can perform similarly to dental amalgams for the first 5 years. But the most remarkable is that composite resin failures may be related to certain individual risk factors, such as genetic variation. (more…)
Aging, Author Interviews, Gender Differences, Genetic Research / 02.11.2017

MedicalResearch.com Interview with: Dr Mandy Peffers BSc MPhil PhD BVetMed FRCVS Wellcome Trust Clinical Intermediate Fellow Institute of Ageing & Chronic Disease Faculty of Health & Life Sciences University of Liverpool Liverpool UK MedicalResearch.com: What is the background for this study? Response: The project was an extension of Louise Pease’s MSc research project in bioinformatics which aimed to re-analyse existing RNA-seq data to determine age related changes in gene expression in musculoskeletal tissues that may lead to the development of degenerative diseases.  From existing literature we identified that degenerative diseases such as osteoarthritis and tendinitis were more prevalent in females and became more frequent following menopause.  We looked at the biology of the cohort we were trying to assess and discovered a gender imbalance, we hypothesised that this was why few results had been obtained from the original analysis. So we developed a research proposal that detailed extending the existing data to publicly available data and merging the experiments; to increase the number of replicates available and balance the experimental design.  We conducted multiple analyses and discovered that splitting samples by age and gender obtained the most significant results, and that whilst in a lot of cases the same genes were being differentially expressed, they were changing in opposite directions.  Louise remembered her statistics lecturer Gerard Cowburn (Ged) taught her about the assumptions of statistical tests, in particular covariance analysis (which has previously been used to show that age and gender do not affect gene expression) assumed that under the conditions being tested data points were not opposites.  Realising that this assumption had been violated by the data she began to think about what other assumptions we were working with and how to test their validity. (more…)
Author Interviews, Genetic Research, PLoS / 07.10.2017

MedicalResearch.com Interview with: Colin Sharpe School of Biology Institute of Biomolecular and Biomedical Science School of Biological Sciences University of Portsmouth Portsmouth, United Kingdom  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have long been fascinated by the question of what underpins the increasing complexity of multicellular animals. In a recent publication we looked at changes to the diversity of the NCoR family corepressors (NCoRs) across the Deuterostomes and found an increase in diversity from sea urchins to humans (1). This is due to gene duplication, an increase in alternative splicing and the encorporation of more protein motifs and domains. In this study we devised a measure of functional diversity based on these three factors and calculated this value for over 12000 genes involved in transcription in nine species from the nematode worm to humans. Orthologues whose increase in diversity correlated with the increase in complexity of these animals were then selected and we looked for common features and interactions between the selected genes. We found that proteins that regulate the dynamic organisation of chromatin were significantly enriched within the selection. (more…)
Author Interviews, Clots - Coagulation, Genetic Research, JAMA, Surgical Research / 04.10.2017

MedicalResearch.com Interview with: Anne R. Bass, MD Associate Professor of Clinical Medicine Weill Cornell Medical College Rheumatology Fellowship Program Director Hospital for Special Surgery New York, NY 10021 MedicalResearch.com: What is the background for this study? Response: Blood thinners are used after orthopedic surgery to prevent blood clots from forming in the legs and traveling to the lungs. They are also used in patients with certain heart diseases to prevent strokes. Blood thinners, like warfarin, are effective but can be associated with serious bleeding complications, especially if the wrong dose is given. Genetic testing can help doctors predict the right warfarin dose to use in an individual patient. In this trial, ≈1600 elderly patients undergoing hip or knee replacement were randomly assigned to receive warfarin dosing based on genetics plus clinical factors (like height, weight and gender), or based on clinical factors alone. The specific genes tested wereVKORC1, CYP2C9, and CYP4F2 which influence warfarin metabolism and the body’s ability to produce clotting factors. (more…)
Author Interviews, Columbia, Genetic Research / 29.09.2017

MedicalResearch.com Interview with: Carlos Eduardo G. Amorim PhD Columbia University Department of Systems Biology Irving Cancer Research Center  MedicalResearch.com: What is the background for this study? Response: More generally, we were interested in understanding the determinants of the frequencies of mutations that cause disease in humans. More specially, we wanted to test if a long-standing theory in population genetics (namely mutation-selection balance) was a good explanation for the observed frequencies of disease mutations in humans. (more…)
Author Interviews, Autism, Genetic Research, JAMA / 27.09.2017

MedicalResearch.com Interview with: Sven Sandin, PhD Assistant Professor Department of Psychiatry Icahn School of Medicine at Mount Sinai New York, NY 10029  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2014, we estimated the heritability of autism to be approximately 50%. Motivating us then was the lack of studies in autism heritability using population based and the findings from a twin-study in California finding the heritability to be substantially lower than the 80-90% estimated in previous studies. Since then continued efforts working with the questions on heritability and environmental factors for autism we found differences between different methods and different samples. When we went back to our previous data we found the heritability of autism to be higher than previously estimated. We found that our previous result was due to a methodological artifact where the adjustment for differences in follow-up used in that manuscript underestimated the heritability. Using methods used in other heritability studies the heritability is now estimated to 84%. Importantly, as previously concluded, there is no support for any ‘shared environmental factors’ in the etiology of autism, e.g. environmental factors shared between two siblings. (more…)
Author Interviews, Gender Differences, Genetic Research, Sexual Health / 22.09.2017

MedicalResearch.com Interview with: Steven Arnocky PhD Faculty of Arts & Science-Psychology Nipissing University Canada  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  - Previous research has linked the facial width-to-height ratio to a number of testosterone-mediated traits, primarily in men, such as aggression and achievement drive. Some research has also linked FWHR to testosterone directly, although this research is less consistent. If testosterone is linked to cranio-facial development then we hypothesized that facial masculinization should therefore correlate with other testosterone-linked traits. In both men and women, there is good evidence that testosterone increases sexual motivation. In two samples of young-adults from two Canadian cities, we found that  facial width-to-height ratio predicted sex-drive, regardless of whether participants were male or female. In the second study (the larger of the two) we also found that FWHR predicted a more unrestricted sociosexual orientation, in other words, attitudes and behavior consistent with more pluralistic mating, as well as more intended infidelity. (more…)
Author Interviews, Diabetes, Flu - Influenza, Genetic Research / 19.09.2017

MedicalResearch.com Interview with: Paz Lopez-Doriga Ruiz MD, PhD candidate Norwegian Institute of Public Health Department of Non Communicable Diseases OsloPaz Lopez-Doriga Ruiz MD, PhD candidate Norwegian Institute of Public Health Department of Non Communicable Diseases Oslo  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Some case reports have linked pandemic influenza to the development of type 1 diabetes. Other studies have suggested that also respiratory infections may contribute to type 1 diabetes risk.  Our findings supports a suggested role of respiratory infections in the etiology of type 1 diabetes and influenza virus could be a contributing factor to the development of clinical diabetes, due to stress and inflammation in predisposed individuals. (more…)
AHA Journals, Author Interviews, Genetic Research / 11.09.2017

MedicalResearch.com Interview with: Bengt Zöller, MD, PhD Associate professor in Internal Medicine Specialist Physician in Clinical Chemistry Specialist Physician in Family Medicine Lund University/ Region Skåne Center for Primary Health Care Research University Hospital, Malmö, Sweden MedicalResearch.com: What is the background for this study? Response: Previous studies have suggested an association between height and venous thromboembolism but association might be confounded. We therefore permed a Nationwide study including a cohort of siblings -a co sibling analysis to adjust for familial confounders (genetic and shared familial environmental factors). (more…)
Author Interviews, Genetic Research, Melanoma / 08.09.2017

MedicalResearch.com Interview with: Rutao Cui, MD/PhD Professor Vice Chair for Laboratory Administration Director, Laboratory of Melanoma Biology Department of Pharmacology and Experimental Therapeutics Professor of Dermatology Boston University Boston, Mass 02118 MedicalResearch.com: What is the background for this study? Response: Red-headed people are making up to 1~2% of the world’s population. They carry “red hair color” variants of MC1R (MC1R-RHC) which are responsible for their characteristic features, including red hair, pale skin, freckles and poor tanning ability. MC1R-RHC also increases risk of melanoma, the deadliest form of skin cancer. People without red hair but with a single copy of MC1R-RHC also have an increased melanoma risk, who may make more than 50% of the northern European population. It is unknown why redheads are more prone to melanoma, and whether the activity of red hair color variants could be restored for therapeutic benefits. (more…)
Author Interviews, Genetic Research, PLoS / 07.09.2017

MedicalResearch.com Interview with: Hakhamanesh Mostafavi, MS PhD student Department of Biological Sciences Columbia University  MedicalResearch.com: What is the background for this study? Response: We know very little about the genetic variants that underlie adaptation in humans. This is in part because we have mostly been limited to methods that search for footprints of ancient selection (that has acted for over thousands to millions of years) in the genomes of present-day humans; so by design are indirect and make strong assumptions about the nature of selection. These days, thanks to advances in genomic technologies, genetic data for large numbers of people is being collected, mostly for biomedical purposes. Accompanied by information on survival and reproductive success of these individuals, such large datasets provide unprecedented opportunities for more direct ways to study adaptation in humans. In this work, we introduced an approach to directly observe natural selection ongoing in humans. The approach consists in searching for mutations that change in frequency with the age of the individuals that carry them, and so are associated with survival. We applied it to around 210,000 individuals from two large US and UK datasets. (more…)
Alzheimer's - Dementia, Author Interviews, Gender Differences, Genetic Research, JAMA / 29.08.2017

MedicalResearch.com Interview with: Arthur W. Toga PhD Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences, Radiology and Engineering Ghada Irani Chair in Neuroscience Director, USC Mark and Mary Stevens Neuroimaging and informatics institute USC Institute for Neuroimaging and Informatics Keck School of Medicine of USC University of Southern California Los Angeles, CA  90032  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ε4 allele of the Apolipoprotein E (APOE) gene is the main genetic risk factor for late-onset Alzheimer's disease.  This study reexamines and corrects the sex-dependent risks that white men and women with one copy of the ε4 allele face for developing Alzheimer's disease using a very large data set of 57,979 North Americans and Europeans from the Global Alzheimer's Association Interactive Network (GAAIN). The study results show that these men and women between the ages of 55 and 85 have the same odds of developing Alzheimer's disease, with the exception that women face significantly higher risks than men between the ages of 65 and 75.  Further, these women showed increased risk over men between the ages of 55 and 70 for mild cognitive impairment (MCI), which is often a transitional phase to dementia. (more…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids, UCLA / 28.08.2017

MedicalResearch.com Interview with: Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease. In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases. Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments. (more…)
Author Interviews, Genetic Research, JAMA, Pancreatic, Surgical Research / 25.08.2017

MedicalResearch.com Interview with: Nancy You, MD, MHSc, FACS Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston  MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was motivated by the emerging promise of precision medicine and the emerging evidence that immunotherapy may have phenomenal efficacy in particular molecular subtypes of cancers.  This specific molecular subtype shows deficiency in DNA mismatch repair mechanisms and therefore is thought to be more immunogenic.  DNA mismatch repair deficiency can arise from germline defects such as in the case of patients with Lynch Syndrome, an inherited cancer syndrome, or from epigenetic inactivation DNA mismatch repair genes. Overall, pancreas cancer has seen limited success with conventional chemotherapy.  In our study, we demonstrated that there is a particular molecular subtype of pancreas cancer that is characterized by defect in DNA mismatch repair genes and by microsatelie instability that has a different prognosis than other pancreas cancers.  This subtype of pancreas cancer is suspected to also respond to immunotherapy. (more…)