Author Interviews, Genetic Research, Heart Disease, Lipids, NEJM, Statins / 13.03.2019

MedicalResearch.com Interview with: Brian A Ference, MD, MPhil, MSc, FACC, FESC Professor and Director of Research in Translational Therapeutics Executive Director, Centre for Naturally Randomized Trials Strangeways Research Laboratory University of Cambridge Cambridge, UK MedicalResearch.com: What is the background for this study? Response: Bempedoic acid is a novel therapy currently in development that lowers LDL-C by inhibiting ATP-citrate lyase, an enzyme in the same cholesterol biosynthesis pathway as HMG-CoA reductase (the target of stains).  However, whether lowering LDL-C by inhibiting ATP-citrate lyase will reduce the risk of cardiovascular events to the same extent as lowering LDL-C by inhibiting HMG-CoA reductase with a statin is unknown. We conducted a “naturally randomized trial” using Mendelian randomization in more than 650,000 participants who experienced more than 100,000 cardiovascular events to evaluate the potential clinical benefit of lowering LDL-C by inhibiting ATP-citrate lyase as compared to lowering LDL-C by inhibiting HMG-CoA reductase. (more…)
Author Interviews, Genetic Research, JAMA, Prostate Cancer / 24.02.2019

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Genetic Research, Smoking, Tobacco / 22.02.2019

MedicalResearch.com Interview with: 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. (more…)
Author Interviews, Genetic Research, OBGYNE / 18.02.2019

MedicalResearch.com Interview with: Zhiyong Zhang PhD Key Laboratory for the Physics and Chemistry of Nanodevices Department of Electronics Peking University Beijing China MedicalResearch.com: What is the background for this study? What are the main findings? Response: Down syndrome is caused by the presence of an extra 21st chromosome within the genome and is the most common birth defect (occurring in approximately 1 in 800 births). In the absence of a multiplexed quantitative diagnostic device, pregnant women have been examined with the ultrasound and the indirect biochemical markers (Alpha-fetoprotein, chorionic gonadotropin and free estriol) which are accompanied with a high misdiagnosis rate. And the diagnostic test (such as amniocentesis) following the wrong screening test results will bring harm to both the pregnant women and the fetuses. Through PCR (polymerization chain reaction) amplification of the fetal DNA in the pregnant mother’s peripheral blood and fluorescence read-out, whole-genome sequencing (WGS)-based non-invasive prenatal testing (NIPT) sequences all the genomic DNA segments in parallel and quantitatively compares the percentage of different chromosomes, which increases the sensitivity for prenatal detection of Down syndrome. However, the complex instrumental setups and the resulted high processing cost present challenges for the large-scale application of WGS-based diagnosis at the point of care in the urban and rural areas of developing countries. Hence, beside the costly WGS method, there is an urgent need to develop a cost-effective NIPT biochip with simple instrumental setting, fast detection speed, high sensitivity, and programmable to multiple disease markers. Taking advantages of we have developed a novel field effect transistor (FET) based biosensor that reveals a fast, ultra-sensitive, highly specific and cost-effective methods and someday can be used to detect fetal Down syndrome in NIPT.  (more…)
Aging, Author Interviews, Genetic Research / 12.02.2019

MedicalResearch.com Interview with: 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. 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. (more…)
Author Interviews, Genetic Research, JAMA, Race/Ethnic Diversity, Stroke / 11.02.2019

MedicalResearch.com Interview with: 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. (more…)
ADHD, Author Interviews, Genetic Research, Mental Health Research, Pediatrics, Schizophrenia / 31.01.2019

MedicalResearch.com Interview with: Silvia Alemany, PhD first author Barcelona Institute for Global Health (ISGlobal), a centre supported by "la Caixa". In collaboration with co-authors: Philip Jansen,MD, MSc and Tonya White, MD, PhD Erasmus University Medical Center, Rotterdam MedicalResearch.com: What is the background for this study? Response: Individuals affected by psychiatric disorders can demonstrate morphological brain abnormalities when compared to healthy controls. Although both genetic and environmental factors can account for these brain abnormalities, we expect that genetic susceptibility for psychiatric disorders has the greatest influence on the development of the brain. Genetic susceptibility for psychiatric disorders can be estimated at the individual level by generating polygenic risk scores. Using this methodology, genetic susceptibility to psychiatric disorders and cognition has been associated with behavior problems in childhood. These findings suggest that heritable neurobiological mechanisms are at play in very early in the course of the illnesses. (more…)
Author Interviews, Cancer Research, Genetic Research, Weight Research / 24.01.2019

MedicalResearch.com Interview with: Brian R. Lane MD PhD Division of Urology Spectrum Health Grand Rapids, Michigan MedicalResearch.com: Can you explain how you conducted your study, and what the main findings were? Response:  We used large-scale genome-wide association studies (GWAS) to identify genetic variants associated with obesity measures, blood pressure, lipids, type 2 diabetes, insulin, and glucose. these genetic variants were used as proxies for the above-mentioned risk factors and evaluated in relation to renal cell carcinoma risk (kidney cancer) using GWAS data from 10,000 RCC patients and 20,000 control participants. -          Based on these genetic data, we found that multiple measures of obesity, as well as diastolic blood pressure (DBP) and fasting insulin, are associated with renal cell carcinoma risk. In contrast, we found little evidence for an association with RCC risk for systolic blood pressure (SBP), circulating lipids, overall diabetes, or fasting glucose.  (more…)
Author Interviews, Genetic Research, Hearing Loss, JAMA, Karolinski Institute / 21.01.2019

MedicalResearch.com Interview with: Christopher R. Cederroth | Ph.D. Docent Associate Professor Experimental Audiology | Department of Physiology and Pharmacology Karolinska Institutet Sweden MedicalResearch.com: What is the background for this study? Response: Tinnitus is experienced is experienced by a large proportion of the population and affects more than 15% of the population worldwide (estimated 70 million people in Europe). However, for near 3% of the population, tinnitus becomes a chronic bothersome and incapacitating symptom. Severe tinnitus interferes with sleep, mood, and concentration and thus impacts life quality, ultimately leading to sick leave and disability pension. A high cost to society has been reported, and since the prevalence of tinnitus has been predicted to double in Europe by 2050, there is an important need for an effective treatment. And today there are none, with the exception of cognitive behavioral therapy, which helps coping with it but does not remove the tinnitus. There has been a number of innovative treatment approaches, but they are overall not successful and it is now agreed that it is likely because tinnitus is a heterogeneous condition – meaning that we cannot consider tinnitus a single entity but an ensemble of different forms or subtypes, which need to be defined. Tinnitus has always been considered a condition influenced by environmental factors, but our initial studies suggested the opposite. Adoption studies are excellent in showing the influence of shared-environment effects and establish a genetic basis for a disease or a trait. It allows to test the transmission of a trait between the adoptee and their biological or their adoptive parent. Transmission via the biological parent is expected to be due to a heritable genetic effect, while transmission via the adoptive parent is associated with home-environment, the so-called shared-environmental effect. We used medical registry data to identify tinnitus patients and adoptees. (more…)
Author Interviews, Genetic Research, University of Pennsylvania / 16.01.2019

MedicalResearch.com Interview with: Arslan Zaidi PhD University of Pennsylvania and Kateryna Makova, Ph.D. Francis R. and Helen M. Pentz Professor Director, Center for Medical Genomics Department of Biology Penn State University University Park, PA 16802 MedicalResearch.com: What is the background for this study? Response: Mitochondria are organelles that are involved in vital functions in eukaryotic cells, e.g., energy production. Even though they carry their own DNA (mitochondrial DNA, or mtDNA), most of the proteins required for mitochondrial function are encoded by the nuclear genome. Thus, mitochondrial and nuclear proteins must work together in a coordinated manner for proper mitochondrial function. These interactions can sometimes be disrupted leading to phenotypic consequences in inter-species and inter-population laboratory crosses of model organisms when the ancestry of the mitochondrial genome is very different from the nuclear genome. While human populations are genetically not very different from each other, it has been suggested that recent admixture between geographically distant populations might also have phenotypic consequences in humans. We investigated whether there is evidence for this in six different recently admixed populations from the Americas. (more…)
Author Interviews, Columbia, Genetic Research, Kidney Disease / 03.01.2019

MedicalResearch.com Interview with: Emily E. Groopman, B.A Departments of Medicine Hammer Health Sciences, and the Department of Epidemiology Columbia University, New York MedicalResearch.com: What is the background for this study? Response: Exome sequencing (ES), targeted capture of the protein-coding segments of the human genome, is quickly becoming a first-line diagnostic tool in clinical medicine, particularly for pediatric disorders and cancer. However, the utility of ES has not been investigated for the majority of constitutional disorders in adults, including for chronic kidney disease (CKD), which collectively affects more than 1 in 10 individuals worldwide. Thus, we performed ES in 3,315 patients with CKD drawn from two independent cohorts, and evaluated the diagnostic yield and the clinical implications of genetic findings. The cohort was predominantly adult (91.6% of patients aged >21 years), ethnically diverse, and encompassed the major CKD subtypes, broadly reflective of the demographic and clinical features of United States CKD patient population. (more…)
Author Interviews, Genetic Research, Nutrition / 18.12.2018

MedicalResearch.com Interview with: Denny Vågerö  PhD MSc CHESS, Centre for Health Equity Studies Department of Public Health Sciences Stockholm University, Stockholm, Sweden MedicalResearch.com: What is the background for this study? What are the main findings? Response: Transgenerational, epigenetic, response, has been shown in studies of animals and plants. Does it apply to humans? Previous findings of associations between grandparents early nutrition and grandchildren’s mortality have been controversial.  Two reasons for this: evidence in human studies has been based on rather small numbers and potential mechanisms are not very well understood. We have tested the hypothesis that there is “a male line transgenerational response” to nutritional events in pre-puberty in a study much larger than previous ones. We find support for this hypothesis in that boys who enjoyed unusually good access to food during their “slow growth period” (aged 9-12 years) seem to transmit a mortality risk on their grandsons but not granddaughters, in particular for cancer. (more…)
Annals Internal Medicine, Author Interviews, Columbia, Genetic Research, Kidney Disease / 27.11.2018

MedicalResearch.com Interview with: Hila Milo Rasouly, PhD Postdoctoral research scientist Ali Gharavi Lab Columbia University MedicalResearch.com: What is the background for this study? Response: Genome sequencing is increasingly used in clinical medicine to help make a clinical diagnosis and make predictions about potential future complications. The diagnostic yield and limitations for different indications are still being worked out.  We are interested in studying the applications of genome sequencing for chronic kidney diseases. It is estimated that 10% of adults have chronic kidney disease (CKD), and amongst them, 10% are caused by single-gene (Mendelian) forms of disease. The American College of Medical Genetics and Genomics developed guidelines on how to interpret genetic variants in order to make a genetic diagnosis. Our lab has been engaged in studying the yield and impact of genetic testing for  CKD, and in the course of our research, we realized that a very large number of individuals have genetic variants that may be classified as pathogenic based on automated application of the guidelines. However, in majority of these cases, the genetic variant was much too frequent in the population to be plausibly disease-causing or did not match up well with the clinical diagnosis. This led us to wonder about the risk of false-positive genetic diagnosis. To analyze this risk for false-positive genetic diagnosis, we analyzed the genome sequence of 7,974 self-reported healthy adults. (more…)
Author Interviews, Autism, Biomarkers, Genetic Research / 12.11.2018

MedicalResearch.com Interview with: Steven D. Hicks, M.D.,Ph.D Department of Pediatrics Penn State College of Medicine Hershey, PA MedicalResearch.com: What is the background for this study? What are the main findings? Response: Since autism has both genetic and environmental underpinnings, my colleagues and I suspected that transcriptional elements (e.g. regulatory RNA molecules) might be different in the saliva of children with autism compared to peers without autism. We used a non-biased approach to analyze saliva from 372 children, and allowed machine learning techniques to inform which RNA elements best predicted autism status. To our surprise, microbial RNA levels and human RNA levels were equally powerful in predicting which children had autism. This may be because some children with autism eat restricted diets, resist tooth brushing, or put foreign objects in their mouths. The end result was a panel of 32 RNAs (20 human and 12 bacterial) that identified autism with 87% accuracy. Interestingly, when we tested the panel in a completely separate set of 84 children (including children from a different geographic region) the accuracy remained 88%.  (more…)
Author Interviews, Genetic Research, NEJM, Pulmonary Disease, Rheumatology / 24.10.2018

MedicalResearch.com Interview with: Joyce S. Lee, MD Associate Professor Director, Interstitial Lung Disease Program Department of Medicine Division of Pulmonary Sciences and Critical Care Medicine University of Colorado School of Medicine MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Rheumatoid arthritis (RA) is a common inflammatory arthritis that can be complicated by interstitial lung disease (ILD). Patients with RA-ILD share clinical characteristics with another ILD called idiopathic pulmonary fibrosis (IPF). Given the similar clinical phenotype, our goal was to see if these lung diseases (IPF and RA-ILD) shared a common genetic risk factor. The MUC5B promoter variant is the most common risk factor (genetic and otherwise) for the development of IPF. Our findings demonstrate the MUC5B promoter variant is also a strong risk factor for the development of RA-ILD among patients with RA. (more…)
Author Interviews, Cognitive Issues, Genetic Research, Heart Disease / 23.10.2018

MedicalResearch.com Interview with: "Pregnancy 1" by operalynn is licensed under CC BY 2.0Heather Boyd, Ph.D. Senior researcher Department of Epidemiology Research Copenhagen Denmark MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have known for a while that women who have had preeclampsia report different types of cognitive impairment (difficulties with short-term memory, attention deficits) in the years and decades after their pregnancies, and there are a few imaging studies suggesting that these women may have more white matter lesions in the brain and more signs of brain atrophy than women with uncomplicated pregnancies. We also know that women who have had preeclampsia are at increased risk of cardiovascular disease in the years and decades after delivery. Taken together, it was not a great leap to hypothesize that women with a history of preeclampsia might also be at increased risk of dementia later in life. However, the existing epidemiological data were unconvincing, possibly because it takes a great deal of power (a very large study population) to study links between two conditions that often occur decades apart. (more…)
Author Interviews, BMJ, Genetic Research, Pain Research, Pediatrics / 17.10.2018

MedicalResearch.com Interview with: "DNA model" by Caroline Davis2010 is licensed under CC BY 2.0Hakon Hakonarson, MD, PhD Corresponding Author Xiao Chang, PhD Lead Author The Center for Applied Genomics Children’s Hospital Philadelphia Philadelphia, Pennsylvania MedicalResearch.com: What is the background for this study? What are the main findings? Response: Migraine is a genetic disorder characterized by recurrent and intense headaches often accompanied by visual disturbances. Genome-wide association studies (GWASs) are a powerful hypothesis-free tool for investigating the genetic architecture of human disease. Currently, multiple GWASs have been conducted on European adults with migraine that have successfully identified several migraine susceptibility genes involved in neuronal and vascular functions. Considering the prevalence of migraines varies across ethnicities, the genetic risk factors may be different in patients of African ancestries and European ancestries. In addition, if migraine presents at an early age (childhood), it may reflect elevated biological predisposition from genetic factors or increased susceptibility to environmental risk factors. We performed the first GWAS to investigate the susceptibility genes associated with migraine in African-American children. The main out come was that common variants at the 5q33.1 locus in the human genome are associated with migraine risk in African-American children. The genetic underpinnings at this locus responsible for this finding are less relevant in patients of European ancestry.  (more…)
Author Interviews, Cannabis, Genetic Research, JAMA, Mental Health Research / 17.10.2018

MedicalResearch.com Interview with: Dr. Nicole Karcher, PhD Post-doctoral scholar with the NIMH Training in Clinical Sciences fellowship Department of Psychiatry Washington University School of Medicine   MedicalResearch.com: What is the background for this study? What are the main findings? Response: For over fifteen years, researchers have debated the role that cannabis use plays in the development of both psychotic disorders as well as subthreshold psychotic symptoms, such as psychotic-like experiences (PLEs). There is still a lack of consensus regarding the nature of the association between cannabis use and psychosis risk, with some research finding evidence for genetic overlap, while other research finds evidence for potentially causal pathways. The current study examined data from twins and siblings from two different samples, the U.S.-based Human Connectome Project and the Australian Twin Registry, with a total of 4,674 participants. Overall, psychotic-like experiences were associated with three separate cannabis use variables [frequent (≥100 times) use, a Cannabis Use Disorder diagnosis, and current cannabis use]. Furthermore, the current research found evidence for both shared genetic and individual-specific contributions to the association between PLEs and these three cannabis use variables. More specifically, while the association between cannabis use and psychotic-like experiences was largely attributable to shared genetic factors, cannabis users were more likely to endorse PLEs in comparison to the relative who used cannabis less.  (more…)
Author Interviews, Genetic Research, PLoS, Smoking, Tobacco Research / 17.10.2018

MedicalResearch.com Interview with: "Photo booth: The Smoking Man" by simpleinsomnia is licensed under CC BY 2.0Pradeep G. Bhide, Ph.D. Professor | Jim and Betty Ann Rodgers Eminent Scholar Chair of Developmental Neuroscience Director, Center for Brain Repair Department of Biomedical Sciences Florida State University College of Medicine Tallahassee, FL MedicalResearch.com: What is the background for this study? What are the main findings? Response: Until now, much attention had been focused on the adverse effects of cigarette smoking by pregnant women on their children’s cognitive development. Some reports suggested that cigarette smoking during pregnancy can produce harmful effects in multiple generations of descendants (transgenerational effects). Not much had been known about the effects of paternal smoking, although more men smoke cigarettes than women. Our study shows that paternal nicotine exposure can be deleterious to the offspring in multiple generations. That is, cognitive function may be compromised in children and grandchildren of a nicotine-exposed male. Of course, our study was done in mice and not men.  However, since studies done in mice on maternal nicotine exposure produced results consistent with studies done in women and children, we believe that he findings from our present study likely can be extrapolated to humans.  (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research, University Texas / 10.10.2018

MedicalResearch.com Interview with: Mohammad Bilal, MD University of Texas Medical Branch MedicalResearch.com: What is the background for this study? Response: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer among adults in the United States and the second leading cause of cancer related deaths. Recent studies have shown an increasing incidence of CRC in younger patients. This has led to increasing interests in identifying patient populations who might be at increased risk of developing CRC. The U.S. Multi-Society Task Force of Colorectal Cancer (MSTF) recommends that CRC screening should begin at age 50 in average-risk persons. However, recently the American Cancer Society (ACS) have published recommendations to begin CRC screening at age 45 years in average risk patient population. These recommendations were primarily based of modeling studies since there is little outcomes data in younger age groups in regards to prevention and detection of CRC. Despite these new recommendations from the ACS, there is limited direct evidence to support CRC screening at a younger age. In our study, we have evaluated the predictors of increased prevalence of adenomas in the 40 to 49-year-old individuals undergoing colonoscopy.  (more…)
Author Interviews, Breast Cancer, Genetic Research / 10.10.2018

MedicalResearch.com Interview with: "JFK Plaza/ Breast Cancer Awareness" by nakashi is licensed under CC BY 2.0Univ.- Prof. Dr. Wolfgang Schreiner Section Biosimulation and Bioinformatics Center for Medical Statistics, Informatics, and Intelligent Systems Medical University of Vienna General Hospital WIEN / AUSTRIA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The choice of correct individualized therapy for breast cancer depends on correct diagnosis: receptors for estrogen, progesterone and HER2 are determined routinely. However 5-10% of these routine diagnostics are inaccurate and may entail suboptimal therapy. We have paved the way for additional diagnostics from gene expression data so as to increase precision of diagnostics. (more…)
Author Interviews, Columbia, Environmental Risks, Genetic Research, Ophthalmology, PLoS / 09.10.2018

MedicalResearch.com Interview with: Andrei V. Tkatchenko, M.D., Ph.D. Associate Professor Columbia University Medical Center Edward S. Harkness Eye Institute New York, NY 10032 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Clear distance vision is rapidly becoming a rare privilege around the world, especially in Asia, due to increasing prevalence of myopia. Although much effort has been directed towards elucidating the mechanisms underlying refractive eye development and myopia, treatment options for myopia are mostly limited to optical correction, which does not prevent progression of myopia or pathological blinding complications often associated with the disease. During early childhood development, the axial length of the eye normally grows to match its optical power in a process called emmetropization, producing focused images on the retina. However, very often environmental and genetic factors lead to a mismatch between the optical power of the eye and its axial length resulting in the development of myopia if eyes grow too long for their optical power. Experimental studies in many animal species suggest that emmetropization is regulated by optical defocus. The eye can compensate for imposed negative and positive optical defocus by increasing or decreasing its growth rate, respectively. However, the molecular mechanisms underlying emmetropization are poorly understood which prevents development of anti-myopia drugs. (more…)
Author Interviews, Genetic Research, Pediatrics / 28.09.2018

MedicalResearch.com Interview with: Barry M. Lester, PhD Center for the Study of Children at Risk Warren Alpert Medical School, Brown University Women and Infants Hospital of Rhode Island Providence, Rhode Island;  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We know from rodent studies that maternal care or nurturing behavior can change the rat pups physiologic response to stress. More nurturing behavior makes it easier for rat pups to relax after stress. Not only that, these changes are permanent, they last into adulthood and there is evidence that these changes can be passed on to the next generation. With animal studies you can unlock the mechanism for this in ways that you can’t do with humans and we know from the rodent studies that the mechanism for these changes has to do with changes in gene activity. Nurturing behavior controls a specific gene that regulates the infant’s physiological response to stress. In other words, we are looking at maternal behavioral programming of a gene that can make, in our case, a human infant less physiologically reactive to stress. The physiological reactivity to stress that we studied was the production of the stress hormone cortisol. Cortisol is part of the body’s flight or fight reaction, the body’s major response to stress and too much or too little cortisol can be harmful and is related to a wide range of mental and physical health disorders in children and adults. The concerns about separating immigrant children from their parents that we read about every day in the paper are based on this same physiological system, where brain structures that control cortisol production are damaged by the stress of separation.  (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA, Yale / 22.09.2018

MedicalResearch.com Interview with: Michael F. Murray, MD, FACMG, FACP Director for Clinical Operations in the Center for Genomic Health Yale School of Medicine MedicalResearch.com: What is the background for this study? Response: Population screening for the cancer risk associated with the BRCA1 and BRCA2 genes has been suggested by some.  We screened a cohort of about 50,000 adult patient volunteers at Geisinger Health System in Pennsylvania for this risk.  (more…)
Aging, Alzheimer's - Dementia, Author Interviews, CMAJ, Genetic Research / 06.09.2018

MedicalResearch.com Interview with: Ruth Frikke-Schmidt, Professor, Chief Physician, MD, DMSc, PhD Department of Clinical Biochemistry Rigshospitalet, Blegdamsvej & Deputy Head Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen MedicalResearch.com: What is the background for this study?   Response: Alzheimer’s disease and other forms of dementia are devastating, neurodegenerative disorders affecting more than 47 million people in 2015, a number projected to triple by 2050 (1,2). Available curative treatments are lacking, and no useful risk prediction tools exist. The potential for prevention is however substantial, emphasized by the recently observed incidence decline in Western societies, likely caused by improved treatment and prevention of vascular risk factors (1,3,4). Population growth and aging, will however triple dementia prevalence by 2050, if no action is taken. Acting now with ambitious preventive interventions, delaying onset of disease by five years, is estimated to halve the prevalence globally (1,5). Despite important preventive efforts over the last decades - resulting in decreased smoking, lower blood pressure and lower cholesterol levels in the general population - physical inactivity, overweight, and diabetes remain threats for our health care system, and in particular for cardiovascular disease and dementia. Intensifying preventive efforts in general is thus of crucial importance, and especially for those patients at highest risk who most likely will benefit the most from early and targeted prevention. Risk stratification and specific treatment goals according to the estimated absolute 10-year risk, has been implemented in cardiovascular disease for years (6,7). There is an un-met need for similar strategies in dementia, underscored by the publication of several randomized multicomponent trials that seem to improve or maintain brain function in at-risk elderly people from the general population (8-10) (more…)
Aging, Author Interviews, Genetic Research, JAMA / 27.08.2018

MedicalResearch.com Interview with: Yi Zeng, Ph.D.| Professor, Center for Study of Aging and Human Development and Geriatrics Division, School of Medicine, Duke University Professor, National School of Development, Chief Scientist of Raissun Institute for Advanced Studies, Peking University Distinguished Research Scholar, Max Planck Institute for Demographic Research Foreign member of the Royal Netherlands Academy of Arts and Science MedicalResearch.com: What is the background for this study? What are the main findings? Response: Sex differences in genetic associations with human longevity remain largely unknown; investigations on this topic are important for individualized healthcare. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, JAMA, Ovarian Cancer / 21.08.2018

MedicalResearch.com Interview with: Ambry GeneticsShuwei Li, PhD Principal Statistical Geneticist Ambry Genetics MedicalResearch.com: What is the background for this study? What are the main findings? Response: Breast cancer is the most commonly diagnosed cancer, while ovarian cancer is the fifth leading cause of death due to cancer, in US women. Since the discovery of BRCA1 and BRCA2, multiple genes have been reported as risk factors; however, it is still unclear whether the known findings represent the complete genetic landscape of breast and ovarian cancers. Our team performed exome sequencing on more than 10,000 breast and/or ovarian cancer patients and nearly 4,000 controls. We observed increased risk of breast cancer associated with PALB2, ATM, CHEK2 and MSH6 genes, and increased risk of ovarian cancer associated with MSH6, RAD51C, TP53 and ATM genes.   (more…)
Aging, Author Interviews, Genetic Research / 15.08.2018

MedicalResearch.com Interview with: Aladdin H. Shadyab, PhD  MS, MPH, CPH Department of Family Medicine and Public Health University of California, San Diego twitter.com/TheDrAladdin MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies have shown that offspring of long-lived parents are not only likely to live longer but to also avoid major chronic diseases (e.g., coronary heart disease), have fewer chronic disease risk factors, and to have better cognitive and physical function in late life. However, few studies have examined parental longevity in relation to an overall measure of successful aging that included reaching old age free of both major diseases and disabilities. The objective of our study was to determine if parental longevity predicted healthy aging, defined as survival to age 90 without any major age-related diseases (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or physical limitations. The participants of our study were from the Women's Health Initiative, a large, longitudinal study among postmenopausal women from the United States. We observed that women whose mothers survived to at least age 90 years were 25% more likely to achieve healthy aging. We also observed that women whose fathers only lived to age 90 did not have increased likelihood of healthy aging. However, women whose mother and father both lived to age 90 were the most likely to achieve healthy aging. (more…)