Aging, Author Interviews, Genetic Research / 26.08.2014

Dr. Manuel Serrano PhD Tumour Suppression Group CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain.MedicalResearch.com Interview with: Dr. Manuel Serrano PhD Tumour Suppression Group CNIO, Melchor Fernandez Almagro 3, 28029 Madrid, Spain. Medical Research: What are the main findings of the study? Dr. Serrano: We investigated the contribution of rare genetic variation to human exceptional longevity (EL, individuals with ≥100 years of age) by exome-sequencing long-lived siblings in three different families where exceptional longevity clustered. We found only one gene that harbored rare variants that was likely to contribute to human longevity across all three families and this gene was the Apolipoprotein B gene (APOB). We further found that the frequency of these rare APOB variants associated with familial exceptional longevity was greater in a cohort of 206 nonfamilial cases of exceptional longevity compared to the control population, though this association did not reach statistical significance. In addition, we found rare variants in many genes within individual families that are likely to contribute to human longevity given previous studies in animals. (more…)
Author Interviews, Breast Cancer, Genetic Research, NEJM / 07.08.2014

Dr Marc Tischkowitz MD PhD University Lecturer (Associate Professor) and Honorary Consultant Physician in Medical Genetics Department of Medical Genetics, University of CambridgeMedicalResearch.com Interview with: Dr Marc Tischkowitz MD PhD University Lecturer (Associate Professor) and Honorary Consultant  Physician in Medical Genetics Department of Medical Genetics, University of Cambridge Medical Research: What are the main findings of the study? Dr. Tischkowitz: The PALB2 gene was first identified in 2006 and linked to breast cancer in 2007 but until now we have not had good breast cancer risk estimates for women who have inherited PALB2 mutations. This study was started in 2009 by an group of research institutions (The PALB2 Interest Group) in Canada, US, Europe (UK, Belgium, Greece, Italy, Finland) and Australia. We studied 362 individuals with PALB2 mutations from 154 families. We found that awomen with a PALB2 mutation will on average have a 35% risk of developing breast cancer by the age of 70, rising to 58% if there is a strong family history. Our study will help clinicians to better advise and manage such women. There are several new aspects.
  • It is by far the largest study to date and provides the most accurate risk estimates for PALB2 mutation carriers.
  • It shows that the breast cancer risk is modified by the family history. (more…)
Author Interviews, Genetic Research, JAMA, Schizophrenia / 31.07.2014

Dr Angelica Ronald Genes Environment Lifespan (GEL) laboratory Centre for Brain and Cognitive Development Department of Psychological Sciences Birkbeck, University of London London WC1E 7HXMedicalResearch.com Interview with: Dr Angelica Ronald Genes Environment Lifespan (GEL) laboratory Centre for Brain and Cognitive Development Department of Psychological Sciences Birkbeck, University of London London WC1E 7HX Medical Research: What are the main findings of the study? Dr. Ronald: Psychotic experiences, such as paranoia, hallucinations and disorganised thinking, are commonly reported by adolescents. Until now it has not been understood whether mild variations in psychotic experiences in the community are part of the same construct as more severe psychotic experiences in adolescence. Our findings suggest that they are. In our study, over 10,000 16-year-old adolescents in England and Wales were assessed on measures of psychotic experiences. The study identified a close link between normal, less frequent psychotic experiences and more severe and frequent experiences in the general population. A classic twin design was employed, which enabled us to conduct analyses investigating the role of genetic and environmental influences on psychotic experiences. The same genetic influences appeared to play a role across the spectrum of severity of psychotic experiences. The study found that psychotic experiences are moderately heritable in adolescence in the general population. This suggests it would be worth directing molecular genetic endeavours towards this area, which has so far received very little attention in terms of causal explanations. We also show that psychotic experiences have considerable environmental influence; in fact, environmental influence appears to play a larger role in causing psychotic experiences in adolescence than for diagnosed psychotic disorders in adults, such as schizophrenia. This result suggests a fruitful avenue will be to tackle what environmental risk factors influence adolescents to have psychotic experiences. (more…)
Author Interviews, Genetic Research, JCEM, Weight Research / 31.07.2014

Dr. Agatha van der Klaauw, PhD Wellcome Trust Postdoctoral Clinical Fellow Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge Metabolic Research Laboratories Addenbrooke's Hospital Cambridge, United KingdomMedicalResearch.com Interview with: Dr. Agatha van der Klaauw, PhD Wellcome Trust Postdoctoral Clinical Fellow Wellcome Trust-MRC Institute of Metabolic Science University of Cambridge Metabolic Research Laboratories Addenbrooke's Hospital Cambridge, United Kingdom   Medical Research: What are the main findings of the study? Dr. van der Klaauw: Obesity occurs when we eat more calories than we burn which is often easy to do as many foods are highly palatable and high in calories. Highly palatable foods such as chocolate trigger signals in the brain that give a feeling of pleasure and reward (sometimes called cravings) which can contribute to overeating. These signals are processed in the reward centres in the brain, where sets of neurons release chemicals such as dopamine. However, very little is known about whether the reward centres of the brain work differently in some people who are overweight. In this study, we were interested in studying overweight people who had a problem with the melanocortin 4 receptor (MC4R) gene. About 1% of obese people have a problem in this gene which contributes to weight gain from a young age. We compared three groups of people: people who were overweight due to a problem in the MC4R gene, people who were overweight but the gene was normal and some people who were normal weight. We performed functional Magnetic Resonance Imaging (fMRI) scans to look at how the reward centres in the brain were activated by pictures of appetizing food such as chocolate cake compared to bland food such as rice or broccoli and non-food items such as staplers. We found that in normal weight people, the reward centres are activated (light up) when they are shown pictures of cake or chocolate and the same was seen in overweight people with a problem in the MC4R gene. But we found that the reward centres were underactive in overweight volunteers (in whom the gene was normal). (more…)
Author Interviews, Genetic Research, Mental Health Research / 30.07.2014

dr_zachary_kaminskyMedicalResearch.com Interview with: Zachary A. Kaminsky, Ph.D. Assistant Professor Johns Hopkins University School of Medicine Department of Psychiatry Baltimore, MD, 21205 Medical Research: What are the main findings of the study? Dr. Kaminsky: A DNA methylation increase at the SKA2 gene was identified and observed across three post mortem brain tissue cohorts and was associated with suicide. The DNA methylation at the SKA2 gene was associated with lower gene expression of the gene. The same association was found in blood allowing us to attempt to predict suicidal behaviors in living individuals. (more…)
Author Interviews, Breast Cancer, Diabetes, Genetic Research, Nature, Vanderbilt / 23.07.2014

MedicalResearch.com Interview with: Qiuyin Cai, M.D., Ph.D. Associate Professor of Medicine Vanderbilt University Medical Research: What are the main findings of the study? Dr. Cai: We conducted a genome-wide association study in East Asians to search for additional genetic changes that are linked to breast cancer development. The study was conducted as part of the Asia Breast Cancer Consortium, which includes 22,780 women with breast cancer and 24,181 control subjects. We found DNA sequence changes in two genes, PRC1 and ZC3H11A, and a change near the ARRDC3 gene were associated with breast cancer risk. These results were also replicated in a large consortium, including 16,003 breast cancer cases and 41,335 control subjects of European ancestry. (more…)
Author Interviews, Breast Cancer, Genetic Research, Nature / 23.07.2014

MedicalResearch.com Interview with Dr Lim Weng Khong Research Fellow, National Cancer Centre Singapore. Medical Research: What are the main findings of the study? Dr Lim Weng Khong: This study uncovered the genetic cause fibroadenomas, which are very common benign breast tumours in women. The team from National Cancer Centre Singapore, Singapore General Hospital and Duke-NUS Graduate Medical School identified a critical gene called MED12 that has frequent durations in a remarkable 60 per cent of fibroadenomas studied. Their findings have been published in the top-ranked journal Nature Genetics. (more…)
Author Interviews, Gastrointestinal Disease, Genetic Research, NEJM, Pediatrics / 03.07.2014

Dr. Daniel AgardhMedicalResearch.com Interview with: Dr. Daniel Agardh M.D., Ph.D Department of Pediatrics Diabetes and Celiac Disease Unit Skåne University Hospital Malmo, Sweden, MedicalResearch: What are the main findings of the study? Dr. Agardh: In this study, we stratify the risk of celiac disease among children according to their HLA genotype and country of residence. We confirm that HLA-DQ2/2 genotype is the major risk factor for early celiac disease, but also show how the risk differs between the participating countries despite of sharing similar HLA risk. This points to the direction of an interaction between HLA and the environment that eventually lead to an autoimmune response in genetic susceptible children. (more…)
Author Interviews, Diabetes, Genetic Research, Nature / 30.06.2014

Dr. Domenico Accili MD Professor of Medicine Department of Medicine Columbia University College of Physicians and Surgeons New York, New York 10032MedicalResearch.com: Interview with Dr. Domenico Accili MD Professor of Medicine Department of Medicine Columbia University College of Physicians and Surgeons New York, New York 10032 MedicalResearch: What are the main findings of the study? Dr. Accili: By switching off a single gene (foxo1), scientists at Columbia University’s Naomi Berrie Diabetes Center have converted human gastrointestinal cells into insulin-producing cells, demonstrating in principle that a drug could retrain cells inside a person’s GI tract to produce insulin. (more…)
ADHD, Author Interviews, Genetic Research, Nature / 19.06.2014

Michele Jacob, Ph.D. Professor of Neuroscience Sackler School of Graduate Biomedical Sciences Tufts UniversityMedicalResearch.com Interview with Michele Jacob, Ph.D. Professor of Neuroscience Sackler School of Graduate Biomedical Sciences Tufts University MedicalResearch: What are the main findings of the study? Dr. Jacob: Autistic-like behaviors and cognitive impairments associate with loss of the Adenomatous Polyposis Coli (APC) gene.  We deleted APC chiefly from excitatory neurons in the mouse developing forebrain; the mice exhibited changes in synapse maturation and density, reduced social interest, increased repetitive behaviors, and learning deficits.  In addition, we found  molecular changes that define a novel role for APC in linking to and regulating the levels of particular proteins that function in synaptic adhesion complexes and signaling pathways that are required for normal learning and memory consolidation. (more…)
Author Interviews, Clots - Coagulation, Genetic Research / 18.06.2014

MedicalResearch.com Interview with: David Ldr_david_l_brown. Brown, MD, FACC Professor of Medicine Cardiovascular Division Washington University School of Medicine St. Louis, MO 63110 MedicalResearch: What are the main findings of the study? Dr. Brown: This meta-analysis of randomized controlled trials showed that using a genotype-based warfarin dosing algorithm did not improve the process or outcomes of anticoagulation compared to using a clinical dosing algorithm. (more…)
Author Interviews, Genetic Research, Mayo Clinic, Schizophrenia / 11.06.2014

Dr. Anders Nykjaer MD, PhD Mayo Clinic in Florida and Aarhus University in DenmarkMedicalResearch.com Interview with: Dr. Anders Nykjaer MD, PhD Mayo Clinic in Florida and Aarhus University in Denmark MedicalResearch: What are the main findings of the study? Dr. Nykjaer: It is well known that ADHD is a complex condition caused by a number of factors including genetic and environment. However, approximately 75% etiology is considered to be genetic and a large body of investigations suggests that it is multiple genes each with a moderate effect that is responsible for conferring susceptibility to ADHD. We have here found one single gene the dysfunction of which is sufficient to trigger the disease.  The gene encodes a receptor, SorCS2, which ensures correct wiring our reward system during embryonic development. Malfunction of the receptor causes ADHD-like symptoms in mice. It is well accepted that ADHD predisposes to psychiatric disorders and genetic reports have linked variations in the SorCS2 gene with schizophrenia. Studies are currently ongoing to evaluate if mutations disrupting the function of SorCS2 may also result in schizophrenia. If this is the case we have come closer to an explanation for the link between ADHD and psychiatric disorders. In the future when prenatal genetic screening becomes established, non-sense mutations in the SorCS2 gene can be used to predict that the child will develop ADHD with 100% certainty.   (more…)
Author Interviews, Genetic Research, OBGYNE / 02.06.2014

MedicalResearch.com Interview with : Dr. Francesco FiorentinoMedicalResearch.com Interview with : Dr. Francesco Fiorentino CEO and Lab Director ROME - ITALY MedicalResearch: What are the main findings of the study? Dr. Fiorentino: This study describes findings from first and second of a three-phase strategy to validate the use of next-generation sequencing (NGS) for comprehensive aneuploidy screening, as a preclinical step toward its routine use in the diagnosis of chromosomal aneuploidy on embryos. The first phase  involved a large preclinical validation study on single cells, and demonstrated that the NGS-based 24-aneuploidy screening protocol was accurate and reliable. The results provided 100% consistency for aneuploid embryo call with array-CGH, the highly validated method of aneuploidy screening. The second phase of the study, instead, focused on the clinical application of the NGS-based protocol for the detection of all chromosomes in embryos. A prospective trial involving analysis of human embryos at the blastocyst stage of development was designed for this purpose, in order to establish similar levels of chromosome-specific NGS copy number assignment concordance compared with 24sure array as those observed in the first phase of the study. Consistency of NGS-based aneuploidy detection was assessed matching the results obtained with array-CGH–based diagnoses, Embryos obtained from 55 consecutive clinical PGS cycles, blindly assessed in parallel with both NGS and array-CGH techniques, displayed 100% concordance for aneuploid embryo call. Consistency obtained during this investigation was similar to those obtained in the first phase of the study that used NGS to examine single cell samples, demonstrating the reliability of the NGS-based method in detection of chromosome aneuploidy also in embryos at blastocyst stage derived from clinical preimplantation genetic screening (PGS)  cycles. The clinical outcomes obtained in this study from preimplantation genetic screening cycles performed with the NGS approach were very encouraging, resulting in a clinical pregnancy rate per embryo transfer of 63.8% (mean age 38.5+2.1 years) and an ongoing implantation rate of 64.0%, values that are comparable with recent results from other comprehensive chromosome screening approaches. In conclusion, the results achieved in this study demonstrate the reliability of the NGS-based protocol for detection of whole chromosome aneuploidies, mosaicism occurrences and segmental changes in embryos. (more…)
Author Interviews, BMJ, Genetic Research, Heart Disease / 22.05.2014

Christopher Labos MD CM, FRCPC, MSc candidate Division of Epidemiology, Biostatistics and Occupational Health McGill University Montreal, Quebec CanadaMedicalResearch.com Interview with: Christopher Labos MD CM, FRCPC, MSc candidate Division of Epidemiology, Biostatistics and Occupational Health McGill University Montreal, Quebec Canada MedicalResearch: What are the main findings of the study? Dr. Labos: A higher genetic risk score (GRS) composed of a set of recently discovered genetic markers strongly linked to cardiovascular disease is associated with an earlier age of first acute coronary syndromes (ACS). We also found that other traditional risk factors such as smoking, obesity and male sex were also associated with an earlier ACS. Two medication classes were also associated with age of first ACS: hormone replacement therapy was associated with earlier ACS while aspirin was associated with ACS occuring at a later age. (more…)
Author Interviews, Endocrinology, Genetic Research, Metabolic Syndrome, Weight Research, Yale / 14.05.2014

MedicalResearch Interview with: Arya Mani, M.D. Department of Internal Medicine and Genetics Yale Cardiovascular Research Center Yale, New Haven CT Arya Mani, M.D. Department of Internal Medicine and Genetics Yale Cardiovascular Research Center Yale, New Haven CT MedicalResearch: What are the main findings of the study? Dr. Mani: Our group has identified a gene that when mutated it causes a form of truncal (central) obesity that is associated with a cluster of coronary artery disease risk factors, including high blood pressure, insulin resistance and possibly elevated blood lipids. These associated risk factors are collectively known as the metabolic syndrome, which may lead to development of diseases such as diabetes and coronary artery disease, both of which were very prevalent in the populations we studied. All identified mutations by our group have been so far gain of function mutations, which means they increased the activity of the gene in pathways related to adipogenesis and gluconeogenesis. (more…)
Author Interviews, Breast Cancer, Genetic Research / 29.04.2014

Dr. Yvonne Bombard, PhD Scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital Assistant Professor, Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of TorontoMedicalResearch.com Interview with: Dr. Yvonne Bombard, PhD Scientist in the Keenan Research Centre of the Li Ka Shing Knowledge Institute of St. Michael's Hospital Assistant Professor, Institute of Health Policy, Management and Evaluation, Faculty of Medicine, University of Toronto MedicalResearch.com: What are the main findings of the study? Dr. Bombard: The main finding of the study is that gene expression profiling tests play a critical role when women with early-stage breast cancer decide whether to have chemotherapy, but many of them do not fully understand what some of the test results mean. For many the gene expression profiling test was the main factor in their treatment decision. The women we interviewed understood the test would indicate whether chemotherapy would be beneficial to them. But many thought the test reflected their unique circumstances and did not understand that their test result was based on larger population statistics. Patients often viewed their gene expression profiling results as providing information that was more scientifically valid, uniquely personalized and emotionally significant than any other information they had received. For many, the test was a transformational element that empowered them, allowed them to feel confident in their decisions and may even have rescued them from unnecessary chemotherapy. Patients described emotionally and socially complex reasons why they valued gene expression profiling testing in making their treatment decisions. Patients valued the test because it provided them with certainty amidst confusion, with options and a sense of empowerment, and with personalized, authoritative information. (more…)
Author Interviews, Dengue, Ebola, Genetic Research, Infections, NEJM, NIH / 24.04.2014

Sergio D. Rosenzweig, MD, PhD Director, Primary Immunodeficiency Clinic (PID-C) LHD, NIAID, NIH Head of the Infectious Diseases Susceptibility Unit at the Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD, 20892MedicalResearch.com Interview with: Sergio D. Rosenzweig, MD, PhD Director, Primary Immunodeficiency Clinic (PID-C) Head of the Infectious Diseases Susceptibility Unit at the Laboratory of Host Defenses, National Institutes of Allergy and Infectious Diseases National Institutes of Health Bethesda, MD, 20892 MedicalResearch.com: What are the main findings of the study? Dr. Rosenzweig: We diagnosed a disease called CDG-IIb in two siblings with severe development issues and very low levels of immunoglobulins, which include infection-fighting antibodies. These children were referred to the NIAID Primary Immunodeficiency Clinic through the NIH Undiagnosed Diseases Program. CDG-IIb is an extremely rare congenital disorder of glycosylation (CDG), with only one other case reported. The genetic defect of the disease disrupts glycosylation, the process for attaching and trimming sugars from proteins. Almost 50% of our proteins have sugars attached, and these are called glycoproteins. They include immunoglobulins and also some viral glycoproteins that are made when cells are infected by a virus. The spread of some viruses, including HIV and influenza, depend on viral glycoproteins in order to infect additional cells and form viral protective shields. We found that this type of virus was less able to replicate, infect other cells, or create adequate protective shields in CDG-IIb patient cells because of the glycosylation defect. In comparison, adenovirus, poliovirus, and vaccinia virus, which either do not rely on glycosylation or do not form protective glycoprotein shields, replicated normally when added to both CDG-IIb and healthy cells. (more…)
Author Interviews, Cancer Research, Genetic Research, Journal Clinical Oncology / 20.04.2014

MedicalResearch.com Interview with: Allison W. Kurian, M.D., M.Sc. Assistant Professor of Medicine and of Health Research and Policy Divisions of Oncology and Epidemiology Allison W. Kurian, M.D., M.Sc. Assistant Professor of Medicine and of Health Research and Policy Divisions of Oncology and Epidemiology and James M. Ford, MD Associate Professor of Medicine Pediatrics and Genetics, Division of Oncology, Stanford University School of MedicineJames M. Ford, MD Associate Professor of Medicine Pediatrics and Genetics, Division of Oncology, Stanford University School of Medicine MedicalResearch.com: What are the main findings of the study? Answer: We found that 11% of women who met standard clinical criteria for BRCA1 and BRCA2 (BRCA1/2) mutation testing, yet had tested negative, actually carried an actionable mutation in another cancer-related gene.  We found that patients were highly motivated to learn about their genetic test results and new recommendations for cancer risk reduction.  Over a short follow-up period, colonoscopy screening resulted in early detection of a tubular adenoma in a patient found to have a high-risk MLH1 mutation, and thus the multiple-gene testing in our study has likely prevented at least one cancer to date.  We conclude that multiple-gene sequencing can benefit appropriately selected patients. (more…)
Author Interviews, Genetic Research, Nature, Social Issues / 14.04.2014

MedicalResearch.com Interview with: Prof Dr Isabelle Mansuy Lab of Neuroepigenetics University/ETH Zürich Brain Research Institute Zürich SwitzerlandProf Dr Isabelle Mansuy Lab of Neuroepigenetics University/ETH Zürich Brain Research Institute Zürich Switzerland MedicalResearch.com: What are the main findings of the study? Prof. Mansuy: The mains findings are that the transmission of the effects of traumatic stress in early life involves small non-coding RNAs in sperm. The study shows that some microRNAs are in excess in the sperm of adult males subjected to trauma during early postnatal life, but are also altered in the brain and in blood, and that these alterations are associated with behavioral and metabolic symptoms including depressive behaviors, reduced risk assessment and altered glucose/insulin metabolism. Injecting sperm RNA in fertilized oocytes reproduces these symptoms and confirm that RNA are the responsible factors. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, NIH / 10.04.2014

Prof. Dr. med. Piotr Lewczuk Head,Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, Department of Psychiatry and Psychotherapy, 91054 Erlangen, GermanyMedicalResearch.com Interview with: Prof. Dr. med. Piotr Lewczuk Head,Lab for Clinical Neurochemistry and Neurochemical Dementia Diagnostics, Universitätsklinikum Erlangen, Department of Psychiatry and Psychotherapy, 91054 Erlangen, Germany MedicalResearch.com: What are the main findings of the study? Prof. Dr. med. Piotr Lewczuk: In our study, we investigated the concentrations of four isoforms of amyloid beta peptides in the blood of healthy young volunteers without memory complains. The participants were stratified into three groups according to their apolipoprotein E (APOE) genotype, which is the mostly investigated and generally accepted genetic risk factor for sporadic Alzheimer’s Disease (AD). It is known that the alterations of the amyloid beta metabolism are the earliest changes in the course of AD, occurring many years (or even decades) before the onset of the clinical symptoms, but it is actually not known how early these alterations start. Correspondingly, we wanted to investigate if healthy persons with genetic risk factor show changes in their amyloid beta metabolism already 30-40 years before the age when AD is usually diagnosed. We did not find any differences between the groups with and without APOE-driven risk, which might be carefully interpreted as no signs of Alzheimer’s Disease pathology in persons at risk at such an early life stage. Taken together, we think that the Alzheimer’s Disease pathology starts some 10-20 years before the beginning of the clinical symptoms, but not earlier. (more…)
Autism, Genetic Research, NEJM, UCSD / 26.03.2014

MedicalResearch.com Interview with: Dr. Erik Courchesne PhD Professor, Department of Neurosciences UC San Diego School of Medicine MedicalResearch.com: What are the main findings of the study? Dr. Courchesne: “Building a baby’s brain during pregnancy involves creating a cortex that contains six layers,” Courchesne said. “We discovered focal patches of disrupted development of these cortical layers in the majority of children with autism.” The authors created the first three-dimensional model visualizing brain locations where patches of cortex had failed to develop the normal cell-layering pattern. The study found that in the brains of children with autism key genetic markers were absent in brain cells in multiple layers. “This defect,” Courchesne said, “indicates that the crucial early developmental step of creating six distinct layers with specific types of brain cells – something that begins in prenatal life – had been disrupted.”  The study gives clear and direct new evidence that autism begins during pregnancy. (more…)
Author Interviews, Dental Research, Genetic Research / 23.03.2014

Dr. Panos N. Papapanou: Professor of Dental Medicine; Chairman, Section of Oral and Diagnostic Sciences Director, Division of Periodontics Section of Oral and Diagnostic Sciences, College of Dental Medicine, Columbia University, New York, NY, USAMedicalResearch.com Interview with: Dr. Panos N. Papapanou: Professor of Dental Medicine; Chairman, Section of Oral and Diagnostic Sciences Director, Division of Periodontics Section of Oral and Diagnostic Sciences, College of Dental Medicine, Columbia University, New York, NY MedicalResearch.com: What are the main findings of the study? Dr. Papapanou: Gene expression signatures in gum tissues obtained from patients with periodontitis identified two fairly robust clusters, suggesting potential differences in pathobiologic processes between the two groups. In addition, the two clusters displayed differences in important features of the disease (e.g., the extent and severity of periodontitis, and the level of colonization by periodontal bacteria). These findings indicate that gene expression patterns may form the basis for a novel, pathobiology-based classification of periodontitis. (more…)
Author Interviews, Case Western, Chemotherapy, Genetic Research, Lung Cancer, UT Southwestern / 22.03.2014

Dr. Azi Gazdar, MD UT Southwestern Medical Center W. Ray Wallace Distinguished Chair in Molecular Oncology Research Hamon Center for Therapeutic Oncology, PathologyMedicalResearch.com Interview with: Dr. Azi  Gazdar, MD UT Southwestern Medical Center W. Ray Wallace Distinguished Chair in Molecular Oncology Research Hamon Center for Therapeutic Oncology, Pathology MedicalResearch.com: What are the main findings of the study? Dr. Gazdar: We describe the characteristics of lung cancers arising in subjects who inherited a germline mutation that predisposes to lung cancer.  The mutation is rare in the general populations, and is inherited equally by both sexes.  However it is a potent predisposing gene, and one third of the never smoking carriers will develop lung cancer.  Thus, about 1% of patients who develop lung cancer carry the germline mutation.  This figure may rise as awareness of the condition and its link to lung cancer is raised among doctors diagnosing lung cancer. However, lung cancers mainly develop in women who are lifetime never smokers.  Lung cancer development is much less common among smokers and men, although accurate figures are not yet available. So the risk among carriers is somewhat similar to the BRCA genes predisposing to breast cancer, where a female carrier has about a 50% lifetime chance of developing breast cancer. The specific germline mutation (known as T790M) occurs in a gene known as epidermal growth factor receptor (EGFR) gene.  Sporadic mutations in this gene usually predict for effective responses to a class of drugs known as tyrosine kinase inhibitors (TKIs), which are widely used in the treatment of lung cancer.  However, the T790M mutation, when it occurs in sporadic tumors not associated with germline inheritance are resistant to TKI therapy.  Thus the prediction is that lung cancers arising in carriers with the germline mutation would also be resistant to TKI therapy. (more…)
Author Interviews, Genetic Research, Lipids, University of Michigan / 19.03.2014

dr_cristen_j_willerMedicalResearch.com Interview with: Cristen J. Willer, PhD Assistant Professor Division of Cardiovascular Medicine, Dept of Internal Medicine Dept of Human GeneticsDept of Computational Medicine and Bioinformatics University of Michigan Ann Arbor, MI 48109-5618 MedicalResearch.com: What are the main findings of the study? Dr. Willer: We wanted to find new genes related to heart disease, so we examined the DNA of approximately 10,000 Norwegian individuals and found 10 genes that are important regulators of blood cholesterol levels. Nine of these were well known to be related to lipids, but one gene was new.  It turned out to be in a region we'd previously noticed to be related to cholesterol, but it was a big region and we hadn't been able to pinpoint the gene yet.  Using this new approach, focusing on DNA differences that result in slightly different proteins in people, we zeroed in on the gene.  We then altered this gene in mice, and saw the predicted changes in cholesterol levels in mice. (more…)
Author Interviews, BMJ, Brigham & Women's - Harvard, Genetic Research, Medical Research Centers, Nutrition, Weight Research / 19.03.2014

Prof. Lu Qi, Assistant Professor, Department of Nutrition Harvard School of Public Health and Channing Division of Network Medicine Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MAMedicalResearch.com Interview with: Prof. Lu Qi, Assistant Professor, Department of Nutrition Harvard School of Public Health and Channing Division of Network Medicine Department of Medicine, Brigham and Women’s Hospital and Harvard Medical School, Boston, MA MedicalResearch.com: What are the main findings of the study? Dr. Lu Qi: In this study, we for the first time provide reproducible evidence from three large cohort studies to show that the association between regular consumption of fried foods and higher BMI was particularly pronounced among people with a greater genetic predisposition to obesity. On the other hand, the adverse genetic effects on BMI were also amplified by consuming more fried foods, the effects among those who ate fried foods more than four times a week was about twice as large compared with those who ate them less than once a week. (more…)
Author Interviews, Genetic Research, Mayo Clinic, Mental Health Research, Nature / 12.03.2014

MedicalResearch.com Interview with: Prof. Dr. Sven Cichon, PhD Director, Division of Medical Genetics University Hospital Basel Human Genomics Research Group Department of Biomedicine University of Basel Basel, Switzerland MedicalResearch.com: What were the main findings of the study? Answer: We have identified two new gene regions that represent pieces of the jigsaw puzzle of genetic and non-genetic factors that lead to the development of bipolar disorder. One is the gene ADCY2 (Adenylate Cyclase 2) which is involved in signal transmission within nerve cells. The other region comprises two genes, both presumably playing a role in neurodevelopmental processes (MIR2113 and POU3F2). Importantly, these results come out of the largest of these kinds of studies so far, involving altogether more than 24,000 people. (more…)
Author Interviews, Blood Pressure - Hypertension, Diabetes, Genetic Research, University of Pennsylvania / 05.03.2014

MedicalResearch.com Interview with: Brendan Keating D.Phil Assistant Professor, Dept of Pediatrics and Surgery, University of Pennsylvania Lead Clinical Data Analyst, Center for Applied Genomics Children's Hospital of Philadelphia,Brendan Keating D.Phil Assistant Professor, Dept of Pediatrics and Surgery, University of Pennsylvania Lead Clinical Data Analyst, Center for Applied Genomics Children's Hospital of Philadelphia Michael V. Holmes, MD, PhD, MSc, BSc, MRCP Transplant Surgery Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USAMichael V. Holmes, MD, PhD, MSc, BSc, MRCP Transplant Surgery Department of Surgery, Perelman School of Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA MedicalResearch.com: What are the main findings of the study? Answer: We found that individuals with a genetically-elevated BMI had higher blood pressure, inflammatory markers, metabolic markers and a higher risk of type 2 diabetes, although there was little correlation with coronary heart disease in this study population of over 34,500 European-descent individuals of whom over 6,000 had coronary heart disease. (more…)
Author Interviews, Genetic Research, JAMA, Weight Research / 18.02.2014

Dr Clare Llewellyn PhD Cpsychol Lecturer in Behavioural Obesity Research Health Behaviour Research Centre Department of Epidemiology and Public Health University College London, LondonMedicalResearch.com Interview with: Dr Clare Llewellyn PhD Cpsychol Lecturer in Behavioural Obesity Research Health Behaviour Research Centre Department of Epidemiology and Public Health University College London, London  MedicalResearch.com: What are the main findings of the study? Dr. Llewellyn:This study indicated that appetite – and, in particular, satiety sensitivity (how quickly you feel full during eating, or how long you remain full after eating) – could be one of the mechanisms through which ‘obesity genes’ influence body weight. We know that body weight has a strong genetic basis, but the mechanisms through which ‘obesity genes’ influence weight are largely unknown. We showed that children with a higher genetic predisposition to obesity (estimated from a score comprising 28 known obesity-related genes) not only had more body fat (a larger BMI and waist circumference), but importantly they were also less sensitive to satiety. (more…)
Alcohol, Author Interviews, Genetic Research, University of Pennsylvania / 14.02.2014

Henry R. Kranzler, MD Professor, Department of Psychiatry Director of the Center for Studies of Addiction. University of Pennsylvania Perelman School of Medicine, PhiladelphiaMedicalResearch.com Interview with: Henry R. Kranzler, MD Professor, Department of Psychiatry Director of the Center for Studies of Addiction. University of Pennsylvania Perelman School of Medicine, Philadelphia MedicalResearch.com: What are the main findings of the study? Dr. Kranzler: The study had two main findings:
  • First, topiramate, at a maximal dosage of 200 mg/day, which is lower than the 300 mg/day used in prior treatment trials, substantially reduced the frequency of heavy drinking and increased the frequency of abstinent days more than placebo. The lower dosage was well tolerated.
  • Second, a variant in a gene that encodes a receptor subunit that binds topiramate moderated the response to topiramate. That is, C-allele homozygotes in the single nucleotide polymorphism rs2832407 in GRIK1, the gene encoding the GluK1 subunit of the kainate receptor, were the subgroup that accounted for the effects of topiramate on heavy drinking. This has important implications for the personalized treatment of alcohol use disorder, in that 40% of people of European ancestry have this genotype and, if confirmed, these findings would make it possible to screen people genetically to select an effective treatment.
(more…)