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…)
Author Interviews, Genetic Research, Mental Health Research / 14.08.2018

MedicalResearch.com Interview with: Prof. Carmen Sandi Director, Brain Mind Institute Laboratory of Behavioral Genetics Brain Mind Institute Ecole Polytechnique Federale de Lausanne Lausanne, Switzerland  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We are interested in understanding how the brain regulates social behaviors and aggression, both in healthy individuals and individuals with psychiatric disorders. In our recent publication in Molecular Psychiatry, we investigated the impact of an alteration in a gene, St8sia2, that plays important roles during early brain development. Alterations in this gene have been linked with schizophrenia, autism and bipolar disorder, and individuals with these disorders frequently present high aggressiveness. In addition, expression of this gene in the brain can be altered by stressful insults during very early life and development. Our study shows that genetic and environmental conditions linked to a reduction in the expression of this neuroplasticity gene during early life can lead to impaired fear learning and associated pathological aggression. We could further reveal that deficits in St8sia2 expression lead to a dysfunction in a receptor in the amygdala (a brain region critically involved in emotionality and fear learning), the GluN2B subunit of NMDA Receptors. This allowed us to target this receptor with D-cycloserine, a drug that facilitates NMDA receptor function. This treatment, when given acutely, ameliorated the capacity to learn from adversity and reduced individuals’ aggressiveness.  (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, Mental Health Research / 31.07.2018

MedicalResearch.com Interview with: The Jackson LaboratoryCatherine Kaczorowski, Ph.D. Associate Professor and Evnin Family Chair in Alzheimer's Research Kristen O’Connell, Ph.D., Assistant Professor Amy Dunn, Ph.D., Postdoctoral Associate The Jackson Laboratory MedicalResearch.com: What is the background for this study? What are the main findings?  Dr. Amy Dunn: “Alzheimer's disease is complex, with both genetic and environmental factors determining symptom onset and disease progression, though our current understanding of how genetic and environmental factors interact to influence disease risk is incomplete. We recently developed a panel of genetically diverse mice carrying human familial AD mutations (AD-BXDs) that better model human AD in order to determine how genetics and diet interact to modify disease onset and severity. We fed a high fat diet to AD-BXDs and monitored metabolic and cognitive function over the duration of the HFD feeding.  We observed accelerated working memory decline in most of the AD-BXD mouse strains, however, the impact of high fat diet on memory was dependent on individual genetic differences across the panel, with some AD-BXD strains maintaining cognitive function on high fat diet (resilient strains). Our data suggest that diet and genetic background interact to mediate vulnerability to AD pathogenesis, and that metabolic factors (e.g. obesity, body composition) that may contribute to cognitive decline differentially in normal aging versus AD. “ (more…)
Author Interviews, Duke, Genetic Research, Neurology, Pediatrics / 30.07.2018

MedicalResearch.com Interview with:  Paul C Marcogliese, Ph.D. Postdoctoral Associate, Laboratory of Dr. Hugo Bellen Department of Molecular and Human Genetics Baylor College of Medicine Houston, Texas 77030 Loren D. Pena, MD PhD Division of Human Genetics Cincinnati Children's Hospital Medical Center Department of Pediatrics University of Cincinnati Cincinnati, OH 45229 MedicalResearch.com: What is the background for this study? What are the main findings? Response: The Undiagnosed Diseases Network (UDN) is a multi-site collaboration across the US that seeks to help diagnose patients with rare disorders that are ill-defined. Dr. Loren D.M. Pena and Dr. Vandana Shashi at the Duke-Columbia clinical site of the UDN had seen a patient with a severe neurological disorder. While the patient had no symptoms at birth, the patient began falling at about 3 years of age, eventually losing motor coordination and developing seizures. In the interim, the regression has progressed to a severely debilitating state. Re-analysis of the participant’s exome data by our site bioinformatician at Columbia (Nicholas Stong) in Dr. David Goldstein’s laboratory revealed a truncating variant in the single exon gene IRF2BPL that could be the candidate disease-causing gene. The UDN clinicians at Duke then contacted the UDN Model Organism Screening Center (MOSC) led by Dr. Hugo Bellen at Baylor College of Medicine and the Howard Hughes Medical Institute for functional analysis. In parallel, four more patients were found with truncating mutations causing a similar disorder though the UDN and GeneMatcher.org. Additionally, two patients with missense variants in IRF2BPL were identified that displayed seizures and some developmental delay or autism spectrum disorder but no motor regression. Work in MOSC by Dr. Paul Marcogliese using fruit flies revealed that the IRF2BPL truncating variants are severe loss of function mutations and one of the missense variants was a partial loss of function. Additionally, it was found that the fruit fly IRF2BPL gene, called pits, is expressed in the neurons of the adult fly brain. Lowering the levels of pits by about 50% in fly neurons leads to progressive behavioural abnormalities and neurodegeneration. By combining the human genetics, bioinformatics and model organism data, IRF2BPL was found to be a novel disease-causing gene in humans. (more…)
Author Interviews, Genetic Research, Osteoporosis, PLoS, Stanford / 29.07.2018

MedicalResearch.com Interview with: Stuart Kim PhD Professor of Developmental Biology, Emeritus Bio-X Affiliated Faculty James H. Clark Center Stanford University  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Osteoporosis is caused by a reduction in bone mass, and leads to a high incidence of bone fracture because the weakened bone is less able to withstand the stress of slips and falls. Osteoporosis affects millions of elderly, is responsible for as many as 50% of fractures in women and 25% of fractures in men over the age of 50, and accounts for $19 billion in annual health care costs in the US. Identification of people with an increased genetic risk for osteoporosis could reduce the incidence of bone fracture. Low BMD is also a risk factor for stress fractures. For athletes and military personnel undergoing harsh rigors of training, stress fractures are common injuries that limit playing time, military effectiveness and competitive success. Using data from UK Biobank, a genome-wide association study identified 1,362 independent SNPs that clustered into 899 loci of which 613 are new. These data were used to train a genetic algorithm using 22,886 SNPs as well as height, age, weight and sex as predictors. Individuals with low genetic scores (about 2% of those tested) showed a 17-fold increase in risk for osteoporosis and about a 2-fold increase in risk of fractures. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 27.07.2018

MedicalResearch.com Interview with: Gregory Carter, PhD Associate Professor at The Jackson Laboratory MedicalResearch.com: What is the background for this study? What are the main findings? Response: Animal models for late-onset Alzheimer’s disease (LOAD) will be of significant benefit for the discovery and characterization of links between specific genetic factors and the molecular pathways associated with the disease. To date, most animal models have been based on rare, early-onset Alzheimer’s disease genes that incompletely capture the complexity of LOAD and have not translated well to therapies. Therefore, developing and utilizing animal models based on genes hypothesized to play a role in LOAD will provide new insights into its basic biological mechanisms.  (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 25.07.2018

MedicalResearch.com Interview with: Gregory Carter, PhD Associate Professor at The Jackson Laboratory MedicalResearch.com: What is the background for this study? What are the main findings? Response: Late-onset Alzheimer’s disease (LOAD) is the most common form of the disease and the major cause of dementia in the aging population. To date, the complex genetic architecture of LOAD has hampered both our ability to predict disease outcome and to establish research models that effectively replicate human disease pathology. Therefore, most basic research into Alzheimer’s disease has focused on early-onset forms caused by mutations in specific genes, which has provided key biological insights but to date has not translated to effective disease preventatives or cures. Our study analyzes both common and rare human genetic variants to identify those significantly associated with .late-onset Alzheimer’s disease, beginning with a large data set from the Alzheimer’s Disease Sequencing Project. We also analyzed RNA sequencing data from post-mortem human and mouse model samples to prioritize candidate genes. We found a new common coding variant significantly associated with disease, in addition to those in genes previously associated with late-onset Alzheimer’s disease. We also found five candidate genes conferring a significant rare variant burden.  (more…)
Author Interviews, Brigham & Women's - Harvard, Genetic Research, Microbiome / 24.07.2018

MedicalResearch.com Interview with: A. Sloan Devlin, PhD Assistant Professor Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School MedicalResearch.com: What is the background for this study? Response: It is known that the microbiome, the collection of bacteria that live in and on our bodies, influences the development of metabolic diseases including diabetes and obesity. The ways in which the microbiome affects host metabolism, however, are poorly understood. One reason for this lack of understanding is because the gastrointestinal tract contains hundreds of species of bacteria producing many different kinds of metabolites. Untangling the effects of these bacteria and the molecules they make is a significant challenge. In this study, we decided to concentrate on a group of metabolites found in the human gut called bile acids. When we eat a meal, these compounds are released into the gastrointestinal tract where they act as detergents that aid in digestion. Once these molecules reach the lower gastrointestinal tract, the gut bacteria residing there chemically modify these compounds, producing a pool of over 50 different bile acids total. Imbalances in this bile acid pool are thought to influence the progression of diet-induced obesity. However, it is unclear which specific bile acids are responsible for either beneficial or detrimental effects on host metabolism. We set out to address this question by first identifying a selective type of bacterial enzyme called a bile salt hydrolase, then by genetically deleting this enzyme from a common gut bacterium and investigating how this change affected host metabolism. (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Prostate Cancer / 23.07.2018

MedicalResearch.com Interview with: Gong-Hong Wei, PhD Professor, Academy Research Fellow Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu University of Oulu, Finland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is the second most common cancer and the fifth leading cause of cancer-related death in men, with more than 1,100,000 new cases diagnosed and 300,000 deaths yearly around the globe. Among the risk factors for prostate cancer development, the genetic heritability of prostate cancer has been reported near 60%. Over the past decade, genome-wide association studies have identified more than 150 independent single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, we know very little mechanisms accounting for these associations. SNP rs11672691 at the chromosome 19q13 locus has been found not only associated with prostate cancer risk but also aggressiveness, a form of prostate cancer often with worse prognosis and eventually progression to incurable stage. However, how this genomic variant accounts for prostate cancer severity remains totally unknown. Here we found the association of rs11672691 with additional clinical features of aggressive prostate cancer in an independent cohort of patients with prostate cancer, and discovered a rs11672691-mediated gene regulatory network including several novel genes, HOXA2, CEACAM21 and PCAT19, likely causing prostate cancer progression to incurable stage. In particular, the risk G (guanine) allele of rs11672691 was associated with higher RNA levels of PCAT19 and CEACAM21, and poor prognosis in prostate cancer patients. Rs11672691 G allele enhances chromatin binding of HOXA2 to regulate the expression of CEACAM21 and PCAT19. Using the CRISPR-Cas9 genome editing method, we revealed that rs11672691 genotype directly influence HOXA2 in regulating PCAT19 and CEACAM21 expression, and prostate cancer cellular phenotype. (more…)