Author Interviews, Genetic Research / 17.05.2019 Interview with: Tove Fall PhD Senior author of the study Associate Professor in Epidemiology Department of Medical Sciences and the Science for Life Laboratory Uppsala University What is the background for this study? What are the main findings?  Response: Dog ownership is common in the Western society but little is known about what actually makes people get a dog. We conducted a twin study to understand whether the genetic make-up has an influence on this choice. We found that more than 50% of the differences in dog ownership is explained by genetic variants.  (more…)
Author Interviews, Genetic Research, PNAS / 02.05.2019 Interview with: Dr. Casey Trimmer, PhD Geneticist, was a post-doctoral fellow at the Monell Center when the research was conducted What is the background for this study?   Response: We detect odors using 400 different types of sensor proteins, called olfactory receptors, in our noses. An odor molecule activates a specific combination of these receptors, and this pattern of activation gives us information on what we're smelling--whether its floral or smoky, intense or weak, and how much we like it. However, how the system translates receptor activation to these perceptual features is largely unknown. Here, we take advantage of the extensive genetic variation in the OR gene family to understand the contribution of individual ORs to odor perception. By studying cases where the function of a particular OR is lost, we can examine what kinds of perceptual alterations occur, allowing us to link receptor to odor and understand what kind of information the receptor is encoding. Data linking genetic variation to perceptual changes exist for only 5 ORs. Here, we examined the perceived intensity and pleasantness of 68 odors in 332 participants. We used next-generation genome sequencing to identify variants in 418 OR genes and conducted a genetic association analysis to relate this variation to differences in odor perception. We then use a cell-based assay to examine receptor function and investigate the mechanisms underlying our associations. Finally, we examined the contribution of single OR genotype, genetic ancestry, age, and gender to variations in odor perception. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA, Technology / 30.04.2019 Interview with: Steven J.M. Jones, Professor, FRSC, FCAHS Co-Director & Head, Bioinformatics Genome Sciences Centre British Columbia Cancer Research Centre Vancouver, British Columbia, Canada and Jasleen Grewal, BSc.Genome Sciences CentreBritish Columbia Cancer Research CentreVancouver, British Columbia, CanadaJasleen Grewal, BSc. Genome Sciences Centre British Columbia Cancer Research Centre Vancouver, British Columbia, Canada What is the background for this study? Response: Cancer diagnosis requires manual analysis of tissue appearance, histology, and protein expression. However, there are certain types of cancers, known as cancers of unknown primary, that are difficult to diagnose based purely on their appearance and a small set of proteins. In our precision medicine oncogenomics program, we needed an accurate approach to confirm diagnosis of biopsied samples and determine candidate tumour types for where the primary site of the cancer was uncertain.  We developed a machine learning approach, trained on the gene expression data of over 10,688 individual tumours and healthy tissues, that has been able to achieve this task with high accuracy. Genome sequencing offers a high-resolution view of the biological landscape of cancers. RNA-Seq in particular quantifies how much each gene is expressed in a given sample. In this study, we used the entire transcriptome, spanning 17,688 genes in the human genome, to train a machine learning method for cancer diagnosis. The resultant method, SCOPE, takes in the entire transcriptome and outputs an interpretable confidence score from across a set of 40 different cancer types and 26 healthy tissues.  (more…)
Author Interviews, Genetic Research, Nutrition, Sugar / 28.04.2019 Interview with: Dr Daniel Hwang PhD Postdoctoral Research Fellow The University of Queensland Diamantina Institute What is the background for this study?   Response: The aim of the this study is to understand the genetic basis of human taste perception. In this international collaboration project, we started by collecting sensory data from twins in the Australia and USA since 2003. Based on the difference in the genetic relatedness between identical and non-identical twins, our previous studies have quantified the amount of genetic influence on sweet taste perception ( as well as the other sensory phenotypes (  (more…)
Author Interviews, Dental Research, Genetic Research / 28.04.2019 Interview with: Katrina Scurrah PhD Senior Research Fellow (Biostatistician), Twins Research Australia, and Melbourne School of Population and Global Health, The University of Melbourne and Honorary Fellow, Murdoch Childrens Research Institute. What is the background for this study? Response: Oral health is an important component of general health and yet dental caries (decay) is still common in children (affecting up to one in three 5-6 year old children in Australia). Although we know that some genetic and lifestyle factors (such as diet) are important risk factors for caries, the relative importance of these is still unclear.  Risk factors from pregnancy and very early childhood (even before teeth appear) might also be important. This study is the first to include prospectively measured data on health and well-being from pregnancy, birth and early childhood in a study of twin children. We analysed data from a cohort of 172 pairs of twin children to assess the effects of genes and environment on susceptibility to dental caries at six years-of-age. (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA, Lipids / 25.04.2019 Interview with: Florian Kronenberg, MD Division of Genetic Epidemiology Department of Medical Genetics, Molecular and Clinical Pharmacology Medical University of Innsbruck, Innsbruck, Austria What is the background for this study? Response: Lp(a) is one of the most prevalent lipoprotein risk factors for cardiovascular disease. Roughly 20% of the general Caucasian population have concentrations above 50 mg/dL and the 10% with the highest concentrations have a 2 to 3-fold increased risk for myocardial infarction. There is strong evidence from genetic studies that high Lp(a) concentrations are causally related to cardiovascular outcomes. Until recently there was no drug available which lowers Lp(a) without any effects on other lipoproteins. This has recently changed by the development of drugs that block the production of Lp(a) in an impressive way. These drugs have to be studied in randomized controlled trials whether they not only lower Lp(a) concentrations but also cardiovascular outcomes. For the planning of such studies it is crucial to estimate the amount of Lp(a) lowering required to show a clinical benefit. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research, Surgical Research / 22.04.2019 Interview with: Valentine N. Nfonsam, MD, MS, FACS Associate Professor of Surgery Program Director, General Surgery Residency Colon and Rectal Surgery Division of Surgical Oncology University of Arizona, Tucson What is the background for this study? What are the main findings? Response: The overall incidence of colon cancer in the United states has gone down in the last few decades. However, there has been a significant increase in the incidence of sporadic colon cancer is young patients (<50 years old). The etiology of this phenomenon is likely multi-factorial. These young patients do present with more advanced disease and with aggressive features. We demonstrated in our study that the colon cancer tumor biology was different between young and older patients. We also singled out a particular gene, Cartilage oligomeric Matrix Protein (COMP) which was significantly over-expressed in young patients and demonstrated its role in cancer proliferation and metastasis and also its potential as a prognostic biomarker since we were able to detect it in plasma. (more…)
Author Interviews, Depression, Genetic Research, JAMA / 19.04.2019 Interview with: Dr Kimberley Kendall MBBCh Wellcome Trust Clinical Research Fellow Professor James Walters MRC Centre for Neuropsychiatric Genetics and Genomics Professor, Division of Psychological Medicine and Clinical Neurosciences Cardiff University What is the background for this study? Response: Copy number variants (CNVs) are the deletion or duplication of large sections of DNA. Large, rare CNVs have been shown to increase the risk of neurodevelopmental disorders including autism spectrum disorder (ASD), intellectual disability (ID), attention deficit/hyperactivity disorder (ADHD) and schizophrenia. However, the impact of these CNVs on risk of depression was unclear from the existing literature. (more…)
Author Interviews, Cancer Research, Genetic Research / 18.04.2019 Interview with: Rachid Karam, PhD Director, Ambry Translational Genomics Lab Ambry Genetics What is the background for this study? Response: DNA genetic testing (DGT) for hereditary cancer genes is now a well accepted clinical practice; however, the interpretation of DNA variation remains a challenge to laboratories and medical providers. RNA genetic testing (RGT) as a supplement to DGT is a means to clarify the clinical actionability of variants in hereditary cancer genes, improving our ability to accurately apply known strategies for cancer risk reduction. (more…)
Author Interviews, Genetic Research, Microbiome / 13.04.2019 Interview with: Kyung Mo Kim Senior research scientist Korea Polar Research Institute. Professor Gustavo Caetano-Anollés Carl R. Woese Institute for Genomic Biology University of Illinois Arshan Nasir Distinguished Fellow Los Alamos National Laboratory in New Mexico What is the background for this study? What are the main findings? Response: Horizontal gene transfer is the process by which unrelated microorganisms can exchange genes. The famous examples would be transfer of antibiotic resistance genes among bacteria that renders many commercially expensive antibiotics useless. From an evolutionary point of view, it complicates our understanding of how bacteria are related since even distantly-related bacteria can share genes and then cluster together on evolutionary trees. Thus better understanding horizontal evolution is important for both public health and our basic understanding of microbial taxonomy and evolution. There are some excellent existing methods of HGT detection that compare DNA features (e.g. GC%, codon usage) or statistical similarity between genomes to identify foreign genes. However, these methods work better to identify recently transferred genes. Transfers that happened millions or billions of years ago cannot be reliably detected since DNA sequences evolve over time during which foreign DNA can become more host-like. That is why we focused our attention on utilizing approaches that are based on sound evolutionary principles. If a gene is horizontally acquired, then a phylogenetic tree of that gene will be different from the reference or known tree of the organisms. The true phylogenetic tree of organisms describes how organisms have descended from a common ancestor through inheritance of genes. If a gene is acquired from a source outside the parents or from an unrelated organism, then there will be a conflict between gene tree and the reference/known species tree. This conflict can be indication of HGT. (more…)
Author Interviews, Epilepsy, Genetic Research, JAMA, Pediatrics / 12.04.2019 Interview with: Dr. Ahmad Abou Tayoun, PhD Clinical Molecular Geneticist Director of the Genetics Laboratory Al Jalila Children’s United Arab Emirates What is the background for this study?   Response: In this study, we provide data in favor of using an exome-based testing approach, where parental samples can be readily accessible, for early onset epilepsy patients. The exome test includes all coding genes in the human genome. Although we perform exome sequencing on those patients, we demonstrate that a first tier analysis should include targeted interpretation of ~100 genes strongly associated with the disease. This analysis provides diagnoses in ~11% of the patients. Follow up parental testing on a limited number of patients (n=15) that had inconclusive results, revealed de novo (new mutations) variant status, leading to upgrade to positive reports in 7 patients and adding ~5% to the overall diagnostic yield. (more…)
Author Interviews, Cancer Research, Genetic Research / 08.04.2019 Interview with: Eunhee Yi, Ph.D. Postdoctoral Associate The Jackson Laboratory What is the background for this study? What are the main findings?  Response: Recurrence after therapy for glioblastoma (GBM) is unavoidable. There are substantial differences among the cells of GBM tumors in the abundance and types of genetic materials. This heterogeneity is a major driver of therapy failure and disease progression. We previously reported that extrachromosomal DNA (ecDNA) elements, which reside outside the linear genome and represent a mechanism to amplify and activate oncogenes, is a potential cause of the increasing genetic diversity in GBM. Our current study is focused on the development of a novel cytogenetic tool to visualize ecDNA to visualize the behavior of these elements in live cells. We have leveraged the unique properties of ecDNA to develop a CRISPR-based “ecDNA tracing toolbox (EDTB)”.  (more…)
Alcohol, Author Interviews, Genetic Research, Nature, University of Pennsylvania / 05.04.2019 Interview with: Henry R. Kranzler, MD Professor of Psychiatry Perelman School of Medicine University of Pennsylvania What is the background for this study? What are the main findings? Response: Alcohol consumption and alcohol use disorder (AUD) are moderately heritable traits.  To date, genome-wide association studies (GWAS) have not examined these traits in the same sample, which limits an assessment of the extent to which genetic variation is unique to one or the other or shared. This GWAS examined a large sample (nearly 275,000 individuals) from the U.S. Veterans Affairs Million Veteran Program (MVP) for whom data on both alcohol consumption and alcohol use disorder diagnoses were available from an electronic health record.  We identified 18 genetic variants that were significantly associated with either alcohol consumption, AUD, or both. Five of the variants were associated with both traits, eight with consumption only, and five with alcohol use disorder only.  (more…)
Author Interviews, Diabetes, Genetic Research, JAMA, Mental Health Research, Schizophrenia / 03.04.2019 Interview with: Prof Sabine Bahn MD PhD MRCPsych FRSB Cambridge Centre for Neuropsychiatric Research Jakub Tomasik, PhD Department of Chemical Engineering and Biotechnology University of Cambridge What is the background for this study? What are the main findings?  Response: Schizophrenia patients are at increased risk of impaired glucose metabolism, yet the comorbidity between the two conditions cannot be fully explained by known risk factors such as obesity, smoking, stress or antipsychotic medication. Previous family and genome-wide studies have suggested that the co-occurrence between schizophrenia and impaired glucose metabolism might be due to shared genetic factors, as exemplified by increased risk of diabetes in first-degree relatives of schizophrenia patients, but the biological mechanisms underlying this association remain unknown. We examined the association between insulin resistance, schizophrenia polygenic risk and response to treatment in 58 drug-naive schizophrenia patients and 58 matched healthy individuals while controlling for a range of demographic (age, gender, body mass index), lifestyle (smoking, alcohol and cannabis use) and clinical (psychopathology scores, treatment drug) factors. We found that insulin resistance, a key feature contributing to the development of type 2 diabetes, significantly correlated with schizophrenia polygenic risk score in patients, with higher genetic risk of schizophrenia associated with increased insulin resistance. Furthermore, we found that patients with higher insulin resistance were more likely to switch medication during the first year of treatment, which implies lower clinical response.  (more…)
Author Interviews, Diabetes, Genetic Research, Heart Disease, Nature / 02.04.2019 Interview with: Eirini Marouli William Harvey Research Institute Barts and The London School of Medicine and Dentistry, Queen Mary University of London, London What is the background for this study?   Response: Epidemiological studies suggest that shorter stature is associated with increased risk of coronary artery disease (CAD) or type 2 diabetes (T2D). It is not clear though whether these associations are causal or there are other factors mediating these effects. When randomized trials are inappropriate or impossible, we can use Mendelian Randomisation as a good alternative to study the causal relationship between a trait and a disease. Here, we examined over 800 places in the human genome known to be associated with adult height and evaluated how genetically predicted height can affect the risk of CAD or T2D. Furthermore, we evaluated the role of several risk factors including, cholesterol, triglycerides, blood pressure, body mass index, fat percentage, socio-economic parameters including education and income as well as lung function. Lung function was assessed by spirometry measures including FEV1: forced expiratory volume in 1 second, FVC: forced vital capacity. (more…)
Author Interviews, Endocrinology, Genetic Research / 24.03.2019 Interview with: Emily J. Gallagher, MD Assistant Professor of Medicine Endocrinology, Diabetes and Bone Disease Icahn School of Medicine at Mount Sinai What is the background for this study? Response: Multiple Endocrine Neoplasia Syndrome Type 2 (MEN2) is an inherited endocrine disorder characterized by the development of pheochromocytoma, medullary thyroid carcinoma (MTC) and parathyroid tumors. It occurs due to activating missense variants in the RET gene. The estimated prevalence of MEN2 is 1 per 30,000 in the general population. Through a collaboration between The Center for Genomic Health, the Charles Bronfman Institute for Personalized Medicine, and the Division of Endocrinology at Mount Sinai, our aim was to investigate the prevalence and clinical manifestations of pathogenic RET variants in the multi-ethnic BioMe Biobank. The BioMe Biobank is an electronic health record-linked biobank with exome sequencing data available for more than 30,000 patients recruited across The Mount Sinai Health System. (more…)
Author Interviews, Genetic Research, Heart Disease, Lipids, NEJM, Statins / 13.03.2019 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 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 Interview with: Masaki Shiota MD, PhD Department of Urology Graduate School of Medical Sciences Kyushu University Fukuoka , Japan 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 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 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 Interview with: Zhiyong Zhang PhD Key Laboratory for the Physics and Chemistry of Nanodevices Department of Electronics Peking University Beijing China 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 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 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 Interview with: Sandro Marini, MD Research Fellow Jonathan Rosand Laboratory Massachusetts General Hospital Boston, MA 02114 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 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 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 Interview with: Brian R. Lane MD PhD Division of Urology Spectrum Health Grand Rapids, Michigan 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 Interview with: Christopher R. Cederroth | Ph.D. Docent Associate Professor Experimental Audiology | Department of Physiology and Pharmacology Karolinska Institutet Sweden 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 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 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 Interview with: Emily E. Groopman, B.A Departments of Medicine Hammer Health Sciences, and the Department of Epidemiology Columbia University, New York 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 Interview with: Denny Vågerö  PhD MSc CHESS, Centre for Health Equity Studies Department of Public Health Sciences Stockholm University, Stockholm, Sweden 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 Interview with: Hila Milo Rasouly, PhD Postdoctoral research scientist Ali Gharavi Lab Columbia University 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…)