Author Interviews, Autism, Genetic Research, Nature, Pediatrics, Schizophrenia / 04.01.2017 Interview with: Dr. Beate St Pourcain MSc, PhD(Cardiff) Genetic Epidemiology School of Oral and Dental Sciences MRC Integrative Epidemiology Unit University of Bristol What is the background for this study? What are the main findings? Response: People with autism and with schizophrenia both have problems interacting and communicating with other people, because they cannot easily initiate social interactions or give appropriate responses in return. On the other hand, the disorders of autism and schizophrenia develop in very different ways. The first signs of Autism Spectrum Disorder (ASD) typically occur during infancy or early childhood, whereas the symptoms of schizophrenia usually do not appear until early adulthood. The researchers asked whether it is possible to disentangle the apparent symptom overlap in ASD and schizophrenia through genetic analyses. As clinical diagnoses relate to the age of onset of a disorder and do not capture multiple developmental stages, the researchers used a trick. They assumed that there is a continuum between normal and abnormal behaviour and captured social communicative competence - the ability to socially engage with other people successfully - in participants of a population-based birth cohort during development. Specifically, the researchers studied the genetic overlap between the risk of having these psychiatric disorders and these measures of social communicative competence. Investigating thousands of genetic variants with small effects across the genome, they showed that genes influencing social communication problems during childhood overlap with genes conferring risk for autism, but that this relationship wanes during adolescence. In contrast, genes influencing risk for schizophrenia were most strongly interrelated with genes affecting social competence during later adolescence, in line with the natural history of the disorder. "The findings suggest that the risk of developing these contrasting psychiatric conditions is strongly related to distinct sets of genes, both of which influence social communication skills, but exert their maximum influence during different periods of development", explained Beate St Pourcain, senior investigator at the Max Planck Institute and lead author of the study. This is consistent with studies showing that genetic factors underlying social communication behaviour also change to some degree during childhood and adolescence. (more…)
Author Interviews, Blood Pressure - Hypertension, Genetic Research, PLoS, Race/Ethnic Diversity, Social Issues / 25.12.2016 Interview with: Connie J. Mulligan, PhD Professor, Department of Anthropology University of Florida Gainesville, FL What is the background for this study? Response: Lance Gravlee (UF Dept of Anthropology, UF Genetics Institute) started this research over 10 years ago. As a cultural anthropologist, Lance uses ethnographic (open-ended questions) interviews and discovered that over half of the participants in our study talked about experiences of discrimination that happened to people close to them. As a geneticist (UF Dept of Anthropology, UF Genetics Institute), I came into the project because I was interested in seeing how genetics and sociocultural stressors, like discrimination, interact. In our project, we look at blood pressure because hypertension is a disease that shows racial disparities and also because it is a complex disease that is caused by both genetic and environmental factors (like discrimination). (more…)
Author Interviews, Electronic Records, Genetic Research, Heart Disease, Lipids, Science / 25.12.2016 Interview with: Michael F. Murray MD Geisinger Health System Danville, PA 17822 What is the background for this study? What are the main findings? Response: The DiscovEHR cohort was formed as a result of a research collaboration between Geisinger Health System and Regeneron Pharmaceuticals. There are over 50,000 patient participants in the cohort who have volunteered to have their de-identified genomic sequence data linked to their de-identified EHR data for research purposes. We report in this paper findings around the identification of 229 individuals (1:256) with pathogenic or likely pathogenic variants in one of the three genes (LDLR, APOB, PCSK9) associated with Familial Hypercholesterolemia (FH). The study found that these individuals are unlikely to carry a diagnosis of FH and are at risk for early coronary artery disease. (more…)
Author Interviews, Cancer Research, Columbia, Genetic Research, Personalized Medicine / 23.12.2016 Interview with: Dr. Kai Wang Zilkha Neurogenetic Institute, University of Southern California Institute for Genomic Medicine, Columbia University What is the background for this study? What are the main findings? Response: Cancer is a genetic disease caused by a small number of “driver mutations” in the cancer genome that drive disease initiation and progression. To understand such mechanism, there are increasing community efforts in interrogating cancer genomes, transcriptomes and proteomes by high-throughput technologies, generating huge amounts of data. For example, The Cancer Genome Atlas (TCGA) project has already made public 2.5 petabytes of data describing tumor and normal tissues from more than 11,000 patients. We were interested in using such publicly available genomics data to predict cancer driver genes/variants for individual patients, and design an "electronic brain” called iCAGES that learns from such information to provide personalized cancer diagnosis and treatment. iCAGES is composed of three consecutive layers, to infer driver variants, driver genes and drug treatment, respectively. Unlike most other existing tools that infer driver genes from a cohort of patients with similar cancer, iCAGES attempts to predict drivers for individual patient based on his/her genomic profile. What we have found is that iCAGES outperforms other tools in identifying driver variants and driver genes for individual patients. More importantly, a retrospective analysis on TCGA data shows that iCAGES predicts whether patients respond to drug treatment and predicts long-term survival. For example, we analyzed two groups of patients and found that using iCAGES recommend drugs can increase patients’ survival probability by 66%. These results suggest that whole-genome information, together with transcriptome and proteome information, may benefit patients in getting optimal and precise treatment. (more…)
Author Interviews, Genetic Research, Lancet, Pediatrics, Schizophrenia / 22.12.2016 Interview with: Dr Lucy Riglin Division of Psychological Medicine and Clinical Neurosciences MRC Centre for Neuropsychiatric Genetics and Genomics Cardiff University School of Medicine Cardiff UK What is the background for this study? What are the main findings? Response: Schizophrenia is a mental disorder that usually occurs after puberty. However, previous research suggests that individuals who go on to develop schizophrenia often presented cognitive, social, behavioural, and emotional impairments in childhood. Our study found that, in a general population sample, genetic risk for schizophrenia was associated with these childhood impairments as early as age 4 years. (more…)
Author Interviews, Genetic Research, Nature, Weight Research / 21.12.2016 Interview with: Prof. Jamal Tazi Institut de Génétique Moléculaire de Montpellier University of Montpellier Montpellier, Cedex, France What is the background for this study? What are the main findings? Response: Intense drug discovery efforts in the metabolic field highlight the need for novel strategies for the treatment of obesity. In this study we have used a novel approach to uncover novel drugs to treat obesity. Our approach is based on the finding that in humans the energy expenditure balance can be controlled by a single gene LMNA gene that can produce two different proteins with opposing effect on energy expenditure. We identified a molecule ABX300 that targets the expression of LMNA gene and favors energy expenditure leading to fat loss. (more…)
Author Interviews, Cancer Research, Colon Cancer, Genetic Research / 17.12.2016 Interview with: Heather Hampel, MS, LGC Associate Director, Division of Human Genetics Associate Director, Biospecimen Research Professor, Internal Medicine Licensed Genetic Counselor The Ohio State University Comprehensive Cancer Center Columbus, OH 43221 What is the background for this study? What are the main findings? Response: This study was part of the Ohio Colorectal Cancer Prevention Initiative, a statewide study being conducted at 50 hospitals that includes universal tumor screening for Lynch syndrome. For the subset of 450 colorectal cancer patients diagnosed under age 50, we performed multi-gene cancer panel testing regardless of the results of their tumor screening for Lynch syndrome since early age of diagnosis is a red flag that a cancer might be hereditary. (more…)
Aging, Author Interviews, Cancer Research, Genetic Research / 16.12.2016 Interview with: Jerry W. Shay PhD Professor Department of Cell Biology, UT Southwestern Medical Center What did you find? Response: Telomeres are the ends of chromosomes and they gradually shortened with every cell division. There have been multiple studies proposing that shortened telomeres correlate with human aging. Most cancers overcome the shortening of telomeres and aging by activating the enzyme, telomerase. Surprisingly, the human telomerase gene (hTERT) is very close to the telomere on chromosome 5p. During human development telomerase is active until about 18 weeks of gestation. It has been a mystery until this present work of what actually causes telomerase to become silenced. We found in this current work that when telomeres are long during development the telomere loops over and helps to silence the telomerase gene. However, as we age and telomeres get progressively shorter, then telomerase becomes permissive for activation and possibly initiation of cancer. This study in part explain why most cancers are in the 65 and older segment of the population. (more…)
Author Interviews, Genetic Research, JAMA / 16.12.2016 Interview with: C. Anthony Blau, M.D. Professor of Medicine, Division of Hematology University of Washington School of Medicine Co-Director, University of Washington Institute for Stem Cell and Regenerative Medicine Director, Center for Cancer Innovation What is the background for this study? What are the main findings? Response: Matching cancer treatment to the molecular composition of a patient’s tumor holds promise for making cancer therapies more effective, and molecular testing for cancer patients has become widespread in recent years. Recently molecular testing of tumor samples has been complemented by blood tests that characterize tumor DNA that has been shed into the bloodstream.  Blood tests are attractive because they are much less invasive than obtaining tumor tissue via biopsies. (more…)
Author Interviews, Breast Cancer, Genetic Research, JAMA / 12.12.2016 Interview with: Dr. Adrian Lee PhD Professor, Department of Pharmacology and Chemical Biology Director, Women's Cancer Research Center University of Pittsburgh Cancer Institute What is the background for this study? What are the main findings? Response: The goal of this study was to understand molecular changes which occur when breast cancers metastasize to the brain, with the eventual of identifying new therapeutic strategies. Brain metastases occur in 10-15% of patients with metastatic breast cancer and are a major clinical challenge. Limited therapeutic options exist for patients with brain metastases. We analyzed molecular changes in pairs of patient-matched primary breast cancers and brain metastases. We found that brain metastases tended to have the same intrinsic subtype as the primary breast cancer, however, there were many genes which changes in gene expression and may represent therapeutic targets. The most common change was an increase in ErbB2/HER2 which can be targeted clinically. (more…)
Author Interviews, Genetic Research, Leukemia, NYU / 11.12.2016 Interview with: Jason Saliba PhD Perlmutter Cancer Center New York University Langone Medical Center New York, NY What is the background for this study? What are the main findings? Response: The outcome for children with acute lymphoblastic leukemia (ALL) has improved dramatically over the last four decades, but the prognosis for those who relapse remains dismal, especially for those who relapse while on therapy. In fact, relapsed disease remains a leading cause of cancer related mortality in children. To date, various studies have discovered a number of somatic alterations that contribute to driving relapse and have provided profound insight into the selective forces that lead to clonal outgrowth of drug resistant populations. However, the timing of the initial emergence of the driving mutations along with the speed of clonal outgrowth is unknown. Whole exome sequencing (WES) was run on available diagnosis, germline (remission), and relapse samples collected from thirteen pediatric ALL patients treated according to Nordic NOPHO ALL protocols. Analyses were then performed to find somatic missense mutations enriched in the relapse samples versus their patient matched diagnosis and/or germline samples. Candidate relapse driving missense mutations were identified as present at high levels (>20%) in the relapse sample, but were undetectable in germline or low to absent in the diagnosis sample. Eight of the thirteen patients contained mutations in genes previously reported to be enriched at relapse. Interestingly, a majority of the patients contained novel candidate relapse specific genes involved in a wide array of cellular processes such as cell adhesion/migration, RNA polymerase II/transcription, circadian rhythm, the unfolded protein response, RNA transport, epigenetic regulation, DNA methylation, and kinases. (more…)
Author Interviews, Genetic Research, Nature, NIH, Weight Research / 09.12.2016 Interview with: Audrey Chu, Ph.D. Division of Intramural Research National Heart, Lung, and Blood Institute (NHLBI), National Institutes of Health What is the background for this study? What are the main findings? Response: Body shape reflects the underlying adipose tissue distributed throughout different compartments of the body (ectopic fat). Variation in ectopic fat is associated with diabetes, hypertension and heart disease. This is mostly independent of overall adiposity. Ectopic fat can be measured using special x-rays procedures such as CT (“CAT scans”) or MRI and can give more information about fat distribution. Fat distribution characteristics can run in families, suggesting that a person’s genes can help determine the amount of fat that can accumulate in different parts of the body. Identifying genes that are associated with ectopic fat can provide insight into the biological mechanisms leading to differences in cardiometabolic disease risk. In order to understand which genes might be involved, we examined genetic variants across the genome and their association with ectopic fat in the largest study of its kind including over 18,000 individuals of four different ancestral backgrounds. Several new genetic regions were identified in association with ectopic fat in addition to confirming previously known regions. The association of the new regions was specific to ectopic fat, since the majority of the regions were not associated with overall or central adiposity. Furthermore, most of these regions were not associated with type 2 diabetes, lipids, heart disease or blood pressure. The major exception was the region surrounding the UBE2E2 gene, which was associated with diabetes. (more…)
Aging, Author Interviews, Genetic Research, JAMA, Macular Degeneration, Ophthalmology / 08.12.2016 Interview with: dr-anneke-i-den-hollanderAnneke I. den Hollander, PhD Department of Ophthalmology and Department of Human Genetics Donders Institute for Brain, Cognition, and Behaviour Radboud University Medical Center Nijmegen, the Netherland What is the background for this study? What are the main findings? Response: Age-related macular degeneration is caused by a combination of genetic and environmental factors. Rare genetic variants in the complement system have been described in AMD, but their effect remains largely unexplored. In this study we aimed to determine the effect of rare genetic variants in the complement system on complement levels and activity in serum. What are the main findings? Response: Carriers of CFI variants showed decreased FI levels, carriers of C9 Pro167Ser had increased C9 levels, while C3 and FH levels were not altered. Carriers of CFH and CFI variants had a reduced ability to degrade C3b, which for CFI was linked to reduced serum FI levels. (more…)
Author Interviews, Genetic Research, Leukemia / 05.12.2016 Interview with: Michelle Churchman, PhD Scientific Manager of Charles Mullighan's laboratory Department of Pathology St Jude Children's Research Hospital What is the background for this study? What are the main findings? Response: The role of IKZF1 alterations in the development of B-progenitor acute lymphoblastic leukemia (B-ALL) and their role in determining poor outcome of treatment has been a long-term focus of our groups. We had previously identified somatic (tumor-acquired) IKZF1 deletions and mutations in high-risk leukemia, and identified several mechanisms by which these mutations drive high-risk leukemia. We also have a long-standing interest in studying inherited genetic risk factors of childhood ALL. In this latest study, our research team identified a family in Germany with a history of B-cell deficiency and B-ALL that had a germline IKZF1 mutation, prompting us to investigate whether inherited IKZF1 variants are related to predisposition to ALL in general. To investigate this, the IKZF1 gene was sequenced from the germline DNA of nearly 5000 patients enrolled on St. Jude Children’s Research Hospital and Children’s Oncology Group front-line ALL trials. We identified 27 unique inherited (germline) IKZF1 variants in 44 patients and found that most of them perturbed the normal functions of the encoded Ikaros transcription factor. Particularly, several of the variants lost the ability to bind DNA and regulate expression of transcriptional targets. We know from previous studies that genes involved in differentiation and adhesion are overexpressed in IKZF1-altered leukemic cells, which results in abnormal adhesion between cells and components of the bone marrow. Many of the variants resulted in increased adhesion. We show that several of these germline variants caused leukemic cells to be less sensitive to drugs. (more…)
Author Interviews, Genetic Research, Lipids, NEJM / 01.12.2016 Interview with: Brian A. Ference, M.D Division of Cardiovascular Medicine Wayne State University School of Medicine Detroit, MI What are the main findings? Response: Lifelong exposure to modestly lower plasma LDL-C levels caused by rare loss-of-function mutations in the PCSK9 gene is associated with a substantially lower lifetime risk of developing cardiovascular disease. This discovery motivated the development of monoclonal antibodies directed against PCSK9 which have now been shown to reduce plasma LDL-C levels by 50-60%. The cardiovascular medicine community is early anticipating the results of two large cardiovascular outcome trials that will determine if lowering LDL-C levels by inhibiting PCSK9 will reduce the risk of cardiovascular events. Because monoclonal antibodies and other therapies directed against PCSK9 are designed to recapitulate the phenotype of PCSK9 loss-of-function mutations, we reasoned that it may be possible to anticipate the efficacy and safety results of the ongoing cardiovascular outcome studies by more precisely characterizing the effect of genetic variants in the PCSK9 gene on the risk of both cardiovascular events and new onset diabetes. To do this, we a constructed genetic score consisting of multiple independently inherited variants in the PCK9 gene to create an instrument that mimics the effect of PCSK9 inhibitors. We then compared the effect of genetic variants that mimic the effect of PCSK9 inhibitors with the effect of genetic variants in the HMGCR gene that mimic the effect of statins to make inferences about the likely effect of PCSK9 inhibitors on the risk of cardiovascular events and new onset diabetes as compared to treatment with a statin. (more…)
Alcohol, Author Interviews, Biomarkers, Genetic Research / 28.11.2016 Interview with: Chunyu Liu, PhD The Population Sciences Branch, Division of Intramural Research The Framingham Heart Study, National Heart, Lung and Blood Institute Framingham, MA Department of Biostatistics Boston University School of Public Health Boston, MA What is the background for this study? What are the main findings? Response: Excessive alcohol consumption contributes to many diseases as well as to injuries and deaths. The lack of reliable measures of alcohol intake is a major obstacle to the diagnosis and treatment of alcohol-related diseases. Our study has identified a group of DNA markers in blood that could provide the basis for a reliable blood test to detect heavy alcohol use. (more…)
Author Interviews, Gastrointestinal Disease, Genetic Research / 23.11.2016 Interview with: Mauro D’Amato Ikerbasque Research Professor Head, Unit of Gastrointestinal Genetics, Department of Gastrointestinal and Liver Diseases BioDonostia Health Research Institute San Sebastian, Spain What is the background for this study? What are the main findings? Response: Irritable bowel syndrome (IBS) is a very common condition, whose underlying pathophysiology is poorly understood. People with IBS often complain certain foods trigger their symptoms and, at least in some patients, incomplete breakdown of carbohydrates may result in malabsorption with diarrhoea, bloating and abdominal pain. At the extreme of the spectrum of such clinical manifestations, this is what happens in a hereditary form of sucrose intolerance, the congenital sucrase-isomaltase deficiency (CSID) due to mutations in the Si gene that lead to defective enzymatic disaccharidase activity in the gut. Because IBS shows genetic predisposition, we tested the hypothesis that mutations and DNA variants affecting SI enzyme function may confer increased risk of IBS. We studied almost 2000 individuals from several clinics from Europe and USA, and found out that rare SI mutations and other more common defective DNA variants are indeed more frequent in patients than healthy controls. (more…)
Author Interviews, Dermatology, Genetic Research / 22.11.2016 Interview with: Prof. Dr. Regina Betz and Dr. Buket Basmanav Ünalan (first author) Institute of Human Genetics University of Bonn Bonn, Germany What is the background for this study? What are the main findings? Response: Up to know, the cause for uncombable hair was totally unknown. We identified now mutations in three genes, all being responsible for uncombable hair syndrome. Of interest, the corresponding proteins, namely, PADI3, TGM3 and TCHH, are all in the same cascade that is responsible for the formation and mechanical strengthening of the hair shaft. (more…)
Author Interviews, Columbia, Genetic Research, OBGYNE / 03.11.2016 Interview with: Sarah Horvath, MD Paula M. Castaño, MD, MPH Anne R. Davis, MD, MPH Columbia University Medical Center What is the background for this study? What are the main findings? Response: Approximately 3% of pregnant women in the United States will receive a prenatal diagnosis of fetal aneuploidy (such as trisomy 21) or fetal structural abnormality (such as cardiac or CNS malformations). Many of these women will undergo abortion. Advances in screening over the past few decades have allowed earlier diagnosis of aneuploidy, but most structural abnormalities cannot be diagnosed until the anatomy ultrasound at 18-20 weeks gestational age because of fixed patterns of fetal development. Our analysis examines gestational age at time of abortion for these two types of fetal diagnosis from 2004-2014. Our main finding was that median gestational age at time of abortion for fetal aneuploidy decreased from 19 weeks to 14 weeks. However, over the same 11 year period, median gestational age at time of abortion for fetal structural abnormalities remained unchanged and at or above 20 weeks gestation. (more…)
ADHD, Author Interviews, Genetic Research, Pediatrics / 01.11.2016 Interview with: Dr. Josephine Elia, M.D. Neuroscience Center Department of Child and Adolescent Psychiatry Nemours/Alfred I. DuPont Hospital for Children What is the background for this study? What are the main findings? Response: Glutamate neurotransmission may play an important role in ADHD and other neuropsychiatric disorders. The purpose of this study is to determine the frequency of genetic mutations involving specific genes (GRM network genes) which influence glutamatergic neurotransmission. A total of 23 study sites across the USA enrolled 1,013 children, aged 6-17 years who had been previously diagnosed with ADHD. Saliva samples were submitted to The Center for Applied Genomics (CAG) at CHOP for analysis of mutations of interest. Information on medical history, including other neuropsychiatric diagnoses and family history as well as areas of academic and social concern were also collected. Overall, the mutation frequency was 22%, with a higher prevalence of 25% observed in patients aged 6-12. When compared to mutation negative ADHD patients, the patients with the mutations of interest were more likely to have concerns about anger control and disruptive behaviors. (more…)
Anemia, Author Interviews, Genetic Research, Hematology / 27.10.2016 Interview with: Peter M. Glazer, MD, PhD Robert E. Hunter Professor of Therapeutic Radiology and Professor of Genetics; Chair, Department of Therapeutic Radiology Yale University What is the background for this study? What are the main findings? Response: It is generally recognized that gene editing in blood stem cells could provide a strategy for treatment of inherited disorders such as sickle cell disease and thalassaemia. Recent excitement has focused on CRISPR/Cas9 technology because of it is so easy to use. However, the CRISPR approach introduces an active DNA cutting enzyme into cells, which can lead to off-target cuts in the genome. As an alternative, we have pursued triplex-forming peptide nucleic acids (PNAs) designed to bind site-specifically to genomic DNA via strand invasion and formation of PNA/DNA/PNA triplexes. PNAs consist of a charge-neutral peptide-like backbone and nucleobases enabling hybridization with DNA with high affinity. PNA/DNA/PNA triplexes recruit the cell’s own DNA repair machinery to initiate site-specific editing of the genome when single-stranded ‘donor DNAs’ are co-delivered as templates containing the desired sequence modification. We found that triplex-forming PNAs substituted at the gamma position yielded high levels of gene editing in blood stem cells in a mouse model of human β-thalassaemia. Injection of thalassemic mice with nanoparticles containing gamma PNAs and donor DNAs ameliorated the disease phenotype, with sustained elevation of blood hemoglobin levels into the normal range and up to 7% β-globin gene correction in stem cells, with extremely low off-target effects. We conclude that the combination of nanoparticle delivery and next generation PNAs may offer a minimally invasive treatment for genetic disorders of the blood that can be achieved safely and simply by intravenous administration. (more…)
Author Interviews, Genetic Research, Menopause / 21.10.2016 Interview with: Carolyn J. Crandall, MD, MS, FACP Professor of Medicine David Geffen School of Medicine at University of California, Los Angeles UCLA Medicine/GIM Los Angeles, California What is the background for this study? What are the main findings? Response: Scientists have suspected that genes may contribute to the risk of getting hot flashes and night sweats, but studies so far have been few in number and only focused on small parts of the human gene code (for example, the gene coding for estrogen receptors). No study has ever comprehensively sampled gene variations that span the entire human genome to look for associations between genetic variation and risk of hot flashes and night sweats. This was the first study of its kind, performed in more than 17.000 postmenopausal women participating in the Women’s Health Initiative Study. We examined 11,078,977 single-nucleotide polymorphisms, or SNPs, which are gene variants, in a genome-wide association study. Our main results were that 14 gene variants (SNPs) that were significantly associated with increased risk of having hot flashes. All of these variants were located in chromosome 4, in the gene that codes for the tachykinin receptor 3. (more…)
Author Interviews, Gastrointestinal Disease, Genetic Research, Hepatitis - Liver Disease, Weight Research / 15.10.2016 Interview with: Annette Schürmann PhD Department of Experimental Diabetology German Institute of Human Nutrition Potsdam-Rehbruecke (DIfE) Nuthetal Germany German Center for Diabetes Research (DZD München-Neuherberg Germany What is the background for this study? Response: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern of liver at two time points, at the age of 6 weeks, (the earlierst time point to distiguish between those that respond to the diet (responder mice) and those that did not (non-responders)), and at the age of 20 weeks. One transcript that was significantly reduced in the liver of responder mice at both time points was Igfbp2. The reason for the reduced expression was an elevated DNA-methylation at a position that is conserved in the mouse and human sequence. The elevated DNA-methylation of this specifc site in human was recently described to associate with elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old mice did not show differences in liver fat content between responder and non-responder mice we conclude that the alteration of Igfbp2 expression and DNA metyhlation occurs before the development of fatty liver. Our data furthermore showed that the epigenetic inhibition of Igfbp2 expression was associated with elevated blood glucose and insulin resistance but not with fatty liver. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 14.10.2016 Interview with: Panagiotis (Panos) Roussos, MD, PhD Assistant Professor Department of Genetics and Genomic Sciences and Department of Psychiatry Icahn Institute for Genomics and Multiscale Biology Friedman Brain Institute Icahn School of Medicine at Mount Sinai The Leon and Norma Hess Center for Science and Medicine New York, NY 10029 What is the background for this study? What are the main findings? Response: Schizophrenia is a complex neuropsychiatric illness and multiple genetic risk factors contribute to the disease. However, it is unclear how these genetic risk factors act and which molecular functions are affected in brain cells of patients with schizophrenia. In this study, we used neurons derived from pluripotent stem cells of patients with schizophrenia and control samples with no history of neuropsychiatric disease. We identified changes related to the way DNA transcribes (a.k.a. gene expression) in schizophrenia compared to controls during activation of the neurons. These changes affect genes that have been genetically associated with schizophrenia. Our study provides evidence that multiple genetic risk factors might lead to schizophrenia because of a damaging effect on the activity of neurons. (more…)
Author Interviews, Dermatology, Genetic Research, Nature / 13.10.2016 Interview with: Richard A. Spritz, M.D. Professor and Director, Human Medical Genetics and Genomics Program University of Colorado School of Medicine. Aurora, CO 80045 USA What is the background for this study? What are the main findings? Response: Vitiligo is an autoimmune disease in which depigmented skin results from destruction of skin melanocytes, with strong epidemiologic association with several other autoimmune diseases that include autoimmune thyroid disease, type 1 diabetes, rheumatoid arthritis, pernicious anemia, systemic lupus erythematosus, and Addison’s disease. In previous genetic linkage and genome-wide association studies (GWAS) of vitiligo patients of European-derived white ancestry (EUR), we identified 27 vitiligo susceptibility loci. In the present study, we carried out a third GWAS of vitiligo in EUR subjects. The combined analysis, with almost 5,000 vitiligo cases and 40,000 non-vitiligo controls, identified a total 23 new confirmed vitiligo loci, as well as seven with suggestive significance. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, PNAS / 12.10.2016 Interview with: Dr. Magdalena Sastre PhD Faculty of Medicine, Department of Medicine Senior Lecturer Imperial College London What is the background for this study? Response: Alzheimer’s disease is the most common neurodegenerative disorder, affecting over 45 million people around the world. Currently, there are no therapies to cure or stop the progression of the disease. Here, we have developed a gene therapy approach whereby we delivered a factor called PGC-1α, which regulates the expression of genes involved in metabolism, inflammation and oxidative stress in the brain of transgenic mice. This factor is also involved in the regulation of energy in the cells, because it controls the genesis of mitochondria and in the generation of amyloid-β, the main component of the neuritic plaques present in the brains of Alzheimer’s disease patients. We have found that the animals with Alzheimer’s pathology treated with PGC-1α develop less amyloid plaques in the brain, perform memory tasks as well as healthy mice and do not have neuronal loss in the brain areas affected by the disease. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, JAMA, Race/Ethnic Diversity / 10.10.2016 Interview with: Dr Tamara Shiner MD PhD Specialist in Neurology Neurology Division Tel Aviv Sourasky Medical Centre What is the background for this study? What are the main findings? Response: Although in the past believed to be sporadic, there is much emerging evidence for a significant genetic contribution to Dementia with Lewy bodies (DLB). Hetrozygosity for common mutations in the GBA gene have been shown to be more frequent among DLB patients and Parkinson's disease patients than in the general population. We found that GBA mutations are in fact exceptionally frequent among Ashkenazi Jewish (AJ) patients with Dementia with Lewy bodies. Our results indicate that one in three of all Ashkenazi DLB patients carry mutations in this specific gene (compared to approximately 6% in the general Ashkenazi Jewish population). We also found that those who carry these mutations have a more severe disease phenotype. (more…)
Author Interviews, Genetic Research, Nature / 08.10.2016 Interview with: Victor Guryev PhD Team Leader European Research Institute for the Biology of Ageing (ERIBA) What is the background for this study? Response: Decoding of human genomes progresses at an enormous speed. Thirteen years after completion of the first human genome reference, we now obtained full genome information for tens of thousands individuals. This number is expected to reach millions in the next few years. Processing this information is a challenge on its own: we learned how to detect small changes such as single nucleotide variants (SNVs), but identification of larger, structural DNA variants (SVs) is far from being perfect. (more…)