Author Interviews, BMJ, Genetic Research, Pain Research, Pediatrics / 17.10.2018

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

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

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

MedicalResearch.com Interview with: "JFK Plaza/ Breast Cancer Awareness" by nakashi is licensed under CC BY 2.0Univ.- Prof. Dr. Wolfgang Schreiner Section Biosimulation and Bioinformatics Center for Medical Statistics, Informatics, and Intelligent Systems Medical University of Vienna General Hospital WIEN / AUSTRIA MedicalResearch.com: What is the background for this study? What are the main findings? Response: The choice of correct individualized therapy for breast cancer depends on correct diagnosis: receptors for estrogen, progesterone and HER2 are determined routinely. However 5-10% of these routine diagnostics are inaccurate and may entail suboptimal therapy. We have paved the way for additional diagnostics from gene expression data so as to increase precision of diagnostics. (more…)
Author Interviews, Brigham & Women's - Harvard, Diabetes, Heart Disease, JACC / 02.10.2018

MedicalResearch.com Interview with: Scott David Solomon, MD Director, Noninvasive Cardiology Professor, Harvard Medical School Brigham and Women's Hospital  MedicalResearch.com: What is the background for this study? What are the main findings?  Response: The sodium glucose transport proteins are known to be important in regulating uptake of glucose. SGLT-1 is predominantly located in the gut and is responsible for uptake of glucose and galactose in the small intestine. Individuals born with severe mutations of this gene have severe malabsorption syndrome. We looked at genetic variants that lead to reduced function of the protein, but not complete loss of function, in a large cohort of individuals in the NIH funded Atherosclerosis Risk in Communities Study. We found that those with mutations in the gene had reduced glucose uptake, as measured by an oral glucose tolerance test, as well as less obesity, diabetes, heart failure and death. (more…)
Author Interviews, Cancer Research, Genetic Research, JAMA, Yale / 22.09.2018

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

MedicalResearch.com Interview with: Ruth Frikke-Schmidt, Professor, Chief Physician, MD, DMSc, PhD Department of Clinical Biochemistry Rigshospitalet, Blegdamsvej & Deputy Head Department of Clinical Medicine Faculty of Health and Medical Sciences University of Copenhagen MedicalResearch.com: What is the background for this study?   Response: Alzheimer’s disease and other forms of dementia are devastating, neurodegenerative disorders affecting more than 47 million people in 2015, a number projected to triple by 2050 (1,2). Available curative treatments are lacking, and no useful risk prediction tools exist. The potential for prevention is however substantial, emphasized by the recently observed incidence decline in Western societies, likely caused by improved treatment and prevention of vascular risk factors (1,3,4). Population growth and aging, will however triple dementia prevalence by 2050, if no action is taken. Acting now with ambitious preventive interventions, delaying onset of disease by five years, is estimated to halve the prevalence globally (1,5). Despite important preventive efforts over the last decades - resulting in decreased smoking, lower blood pressure and lower cholesterol levels in the general population - physical inactivity, overweight, and diabetes remain threats for our health care system, and in particular for cardiovascular disease and dementia. Intensifying preventive efforts in general is thus of crucial importance, and especially for those patients at highest risk who most likely will benefit the most from early and targeted prevention. Risk stratification and specific treatment goals according to the estimated absolute 10-year risk, has been implemented in cardiovascular disease for years (6,7). There is an un-met need for similar strategies in dementia, underscored by the publication of several randomized multicomponent trials that seem to improve or maintain brain function in at-risk elderly people from the general population (8-10) (more…)
Author Interviews, Cancer Research, Dermatology, Science / 01.09.2018

MedicalResearch.com Interview with: Dr Andrew South, PhD, Associate Professor in the department of Dermatology and Cutaneous Biology at Jefferson (Philadelphia University + Thomas Jefferson University)  MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by Butterfly Syndrome or recessive dystrophic epidermolysis bullosa? Response: Epidermolysis Bullosa, or EB, is a group of genetic diseases caused by mutations in genes which play a role in maintaining skin integrity. An EB patients’ skin can be very fragile which has been likened to butterfly wings, which are also very fragile. Skin blisters are common in EB patients and in some cases large wounds can result from the slightest mechanical trauma, hence the term Butterfly Syndrome. Skin cancer is a major complication of patients with the recessive dystrophic subtype of EB, known as recessive dystrophic epidermolysis bullosa or RDEB, and these cancers, called squamous cell carcinoma (SCC), are very aggressive. SCC is the leading cause of death in patients with RDEB. SCC also arise very early, affecting RDEB patients in their 20’s and 30’s. Our study used genetic analysis of cancers collected from patients to try and determine what causes the cancer at such an early age and what causes these cancers to be so fatal. Skin SCC arising in the general population as a result of sun exposure are generally benign and occur much later in life, regular skin SCC patients are predominantly over the age of 60, therefore something must be different about RDEB SCC.  (more…)
Aging, Author Interviews, Genetic Research, JAMA / 27.08.2018

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

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

MedicalResearch.com Interview with: Aladdin H. Shadyab, PhD  MS, MPH, CPH Department of Family Medicine and Public Health University of California, San Diego twitter.com/TheDrAladdin MedicalResearch.com: What is the background for this study? What are the main findings? Response: Previous studies have shown that offspring of long-lived parents are not only likely to live longer but to also avoid major chronic diseases (e.g., coronary heart disease), have fewer chronic disease risk factors, and to have better cognitive and physical function in late life. However, few studies have examined parental longevity in relation to an overall measure of successful aging that included reaching old age free of both major diseases and disabilities. The objective of our study was to determine if parental longevity predicted healthy aging, defined as survival to age 90 without any major age-related diseases (coronary heart disease, stroke, diabetes, cancer, or hip fracture) or physical limitations. The participants of our study were from the Women's Health Initiative, a large, longitudinal study among postmenopausal women from the United States. We observed that women whose mothers survived to at least age 90 years were 25% more likely to achieve healthy aging. We also observed that women whose fathers only lived to age 90 did not have increased likelihood of healthy aging. However, women whose mother and father both lived to age 90 were the most likely to achieve healthy aging. (more…)
Author Interviews, Biomarkers, Cancer Research, Gastrointestinal Disease, JAMA / 10.08.2018

MedicalResearch.com Interview with: Wei Zhang, Ph.D. Hanes and Willis Family Professor in Cancer Director Cancer Genomics and Precision Oncology Wake Forest Baptist Comprehensive Cancer Center Winston-Salem, NC  27157-1082 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Gastric cancer is a leading cause of cancer-related death worldwide. Infection by the Helicobacter pylori is the major cause of gastric cancer, which accounts for more than 60% of cases. Despite progress in helicobacter pylori eradication and early cancer diagnosis, the five-year survival rate of gastric cancer remains less than 30%. Gastric cancer is one of the most common cancer types in Asia but the incidence for gastric cancer has seen a steadily increase in the United States in recent years. Immunotherapy treatment has shown remarkable benefit for some cancer patients whereas others experience toxicities. It is important to identify markers that help oncologists decide which patient would benefit from this promising new treatment strategy. It has been suggested that gastric cancer that is positive for Epstein-Barr Virus is likely more responsive to immunotherapy but only about 10% of gastric cancer patients belong to this category. More potential markers are urgently needed for clinical practice. There is accumulating evidence that high tumor mutation load, which means there are high numbers of gene mutations in the tumor, can provide a signal to activate immune response systems thus rendering tumors more sensitive to immunotherapy. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, Mental Health Research / 31.07.2018

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

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

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

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

MedicalResearch.com Interview with: Gregory Carter, PhD Associate Professor at The Jackson Laboratory MedicalResearch.com: What is the background for this study? What are the main findings? Response: Late-onset Alzheimer’s disease (LOAD) is the most common form of the disease and the major cause of dementia in the aging population. To date, the complex genetic architecture of LOAD has hampered both our ability to predict disease outcome and to establish research models that effectively replicate human disease pathology. Therefore, most basic research into Alzheimer’s disease has focused on early-onset forms caused by mutations in specific genes, which has provided key biological insights but to date has not translated to effective disease preventatives or cures. Our study analyzes both common and rare human genetic variants to identify those significantly associated with .late-onset Alzheimer’s disease, beginning with a large data set from the Alzheimer’s Disease Sequencing Project. We also analyzed RNA sequencing data from post-mortem human and mouse model samples to prioritize candidate genes. We found a new common coding variant significantly associated with disease, in addition to those in genes previously associated with late-onset Alzheimer’s disease. We also found five candidate genes conferring a significant rare variant burden.  (more…)
Author Interviews, Biomarkers, Cancer Research, Genetic Research, Prostate Cancer / 23.07.2018

MedicalResearch.com Interview with: Gong-Hong Wei, PhD Professor, Academy Research Fellow Faculty of Biochemistry and Molecular Medicine, Biocenter Oulu University of Oulu, Finland MedicalResearch.com: What is the background for this study? What are the main findings? Response: Prostate cancer is the second most common cancer and the fifth leading cause of cancer-related death in men, with more than 1,100,000 new cases diagnosed and 300,000 deaths yearly around the globe. Among the risk factors for prostate cancer development, the genetic heritability of prostate cancer has been reported near 60%. Over the past decade, genome-wide association studies have identified more than 150 independent single nucleotide polymorphisms (SNPs) associated with prostate cancer risk. However, we know very little mechanisms accounting for these associations. SNP rs11672691 at the chromosome 19q13 locus has been found not only associated with prostate cancer risk but also aggressiveness, a form of prostate cancer often with worse prognosis and eventually progression to incurable stage. However, how this genomic variant accounts for prostate cancer severity remains totally unknown. Here we found the association of rs11672691 with additional clinical features of aggressive prostate cancer in an independent cohort of patients with prostate cancer, and discovered a rs11672691-mediated gene regulatory network including several novel genes, HOXA2, CEACAM21 and PCAT19, likely causing prostate cancer progression to incurable stage. In particular, the risk G (guanine) allele of rs11672691 was associated with higher RNA levels of PCAT19 and CEACAM21, and poor prognosis in prostate cancer patients. Rs11672691 G allele enhances chromatin binding of HOXA2 to regulate the expression of CEACAM21 and PCAT19. Using the CRISPR-Cas9 genome editing method, we revealed that rs11672691 genotype directly influence HOXA2 in regulating PCAT19 and CEACAM21 expression, and prostate cancer cellular phenotype. (more…)
Author Interviews, Breast Cancer, Cancer Research, Genetic Research, Nature / 23.07.2018

MedicalResearch.com Interview with: Luca Magnani, Ph.D CRUK Fellow/Senior Research Fellow Department of Surgery and Cancer Imperial Centre for Translational and Experimental Medicine Room 140 1st floor ICTEM building Imperial College Hammersmith London, UK MedicalResearch.com: What is the background for this study? Would you briefly explain what is meant by the Yin Yang1 molecule? Response: This study was designed to investigate the evidence of non-genetic mechanisms that could contribute to breast cancer biology. Specifically, we developed a map of regulatory regions from luminal breast cancer patients. Regulatory regions are pieces of DNA that are not transcribed into protein-coding genes but they provide information about where and how much each gene should be activated. It is worth highlighting that cancer is not only the consequence of gene mutations but also the result of the wrong genes expressed at the wrong time.  To catalogue regulatory regions we looked for specific modifications that are strongly associated with their activity (epigenetic modifications). Doing so we developed the first extensive catalogue  of non-coding DNA regions that might play an essential role in regulating how breast cancer cell behaves. Regulatory regions do their job by interacting with specific molecules called transcription factors. These molecules can read the information stored in these regulatory regions and contribute to regulate gene expression. Yin Yang 1 is one of such molecules and was previously thought as a ambiguous player capable of activating or repressing gene activity.   (more…)
Author Interviews, Genetic Research, Weight Research / 21.07.2018

MedicalResearch.com Interview with: “In-N-Out meal #1” by Chris Makarsky is licensed under CC BY 2.0Dr. Christina Holzapfel PhD Junior Research Group Leader at Institute for Nutritional Medicine Technical University of Munich MedicalResearch.com: What is the background for this study? What are the main findings? Response: A lot of articles about genetic factors and nutritional intake have been published in the last years. Findings are inconsistent and it is not clear, whether genetic variants, especially associated with body mass index, are associated with nutritional intake. Therefore we performed a systematic literature search in order to get an overview about the association between single nucleotide polymorphisms and total energy, carbohydrate and fat intakes. We identified about specific search terms and their combinations more than 10,000 articles. Of these, 39 articles were identified for a relationship between genetic factors and total energy, carbohydrate, or fat consumption. In all studies, we most frequently encountered the fat mass and obesity (FTO) associated gene as well as the melanocortin 4 receptor gene (MC4R). There are indications of a relationship between these two genes and total energy intake. However, the evaluation of the studies did not provide a uniform picture. There is only limited evidence for the relationship between the FTO gene and low energy intake as well as between the MC4R gene and increased energy intake. (more…)
Addiction, Author Interviews, Cocaine, Genetic Research / 17.07.2018

MedicalResearch.com Interview with: “Cocaine concealed in washing powder” by The National Crime Agency is licensed under CC BY 2.0 MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Drug addiction is a chronically relapsing neuropsychiatric disease that affects 15.5 million people in Europe at a cost of 65.7 billion euros per year. All addictive drugs have in common to cause an artificial increase in the release of a neurotransmitter called dopamine, a very basic effect that can be found in all studied animal species from the fly to the man. The release of dopamine takes place in a region of the brain called the ventral striatum, or Nucleus Accumbens (NAc), which is directly involved in reward and reinforcement processes. An excess of dopamine release by the dopaminergic neurons projecting to the NAc from the Ventral Tegmental Area (VTA) triggers long-term changes in the brain, which can lead to addiction. Cocaine is a prototypical addictive drug, since it is heavely abused in Western societies and extensively studied in animal models as well as humans. We discovered that mice lacking the Maged1 gene showed a marked decrease in cocaine-elicited release of dopamine in the NAc and were entirely unresponsive to cocaine at behavioral level. In fact, they did not show any behavioral reaction normally observed after cocaine treatment, such as cocaine-elicited hyperlocomotion, sensitization (an increased effect of the drug following repeated administrations) or addictive behaviors, such as increased preference for places where the animal expects to obtain a cocaine reward or cocaine self-administration. In a subsequent set of experiments, the researchers tried to identify what brain regions are responsible for Maged1 influence on cocaine effects and found that Maged1 expression is specifically required in the prefrontal cortex, and not in the neurons producing dopamine in the VTA, for the development of cocaine sensitization and dopamine release.  (more…)
Aging, Author Interviews, Genetic Research / 09.07.2018

MedicalResearch.com Interview with: “siblings” by Katina Rogers is licensed under CC BY 2.0Stacy L. Andersen, PhD Assistant Professor of Medicine Project Manager New England Centenarian Study Long Life Family Study Boston University School of Medicine Boston Medical Center Boston, MA 02118 MedicalResearch.com: What is the background for this study? Response: Exceptional longevity appears to run in families. Previous studies have found that people who have siblings who live into their 90s or who reach 100 years of age have a greater chance themselves of living longer than the general population. Yet it is supercentenarians, those who reach the age of 110 years, who represent the true extreme of the human lifespan.  We wanted to determine whether the parents and siblings of supercentenarians were more likely to reach very old ages than family members of younger centenarians. We collected family tree information for 29 participants of the New England Centenarian Study aged 110-119 years. Proof of age documents and familial reconstruction methods were used to validate ages and dates of birth and death of the supercentenarian as well as his or her parents and siblings. Mean age at death was compared to birth year and sex-specific US and Swedish cohort life table estimates conditional on survival to age 20 for siblings to omit deaths due to nonheritable factors such as infectious disease or accidents and survival to age 50 (the approximate age at which women are no longer able to reproduce) for parents.  (more…)
Alcohol, Author Interviews, Endocrinology, Genetic Research / 28.06.2018

MedicalResearch.com Interview with: Toni Pak, Ph.D. Professor and Department Chair Department of Cell and Molecular Physiology Loyola University Chicago Maywood, Ill  MedicalResearch.com: What is the background for this study? Response: We have known for many years that drinking alcohol during pregnancy can lead to developmental delays and birth defects in offspring. However, our data demonstrate that drinking large quantities of alcohol in a “binge” fashion before pregnancy can also impact future offspring and importantly, this is true for drinking behaviors of both parents, not just the mother. Our previous data support the idea that alcohol is affecting the parental sperm and eggs to induce these modifications in the offspring, but this most recent work shows the extent of those effects on social behavior, pubertal maturation, and stress hormones as the offspring grow to adulthood. This means that the risky behaviors of young people, such as the extremely popular practice of binge drinking, have potentially far-reaching consequences for generations to come. (more…)
Author Interviews, Heart Disease, JAMA, Lipids / 21.06.2018

MedicalResearch.com Interview with: Dr. Stephen Burgess PhD Programme Leader at the Medical Research Council Biostatistics Unit University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: Lipoprotein(a) is a lipoprotein subclass, and an important biomarker for coronary heart disease. As a clinical biomarker, it has a similar story to LDL-cholesterol (“bad” cholesterol), in that it is thought to be a causal risk factor for coronary heart disease, and so is a potential target for drug development. However, while drugs that lower LDL-cholesterol, such as statins, have been successful in reducing coronary heart disease risk, drugs that lower lipoprotein(a) have not as yet been successful. New drugs are currently in development that specifically target lipoprotein(a) and can lower lipoprotein(a) concentrations by 80-90%. We performed this study to investigate whether these drugs are likely to be successful in reducing coronary heart disease risk. We compared individuals with naturally-occurring genetic variants that predispose them to a higher or lower lifetime concentration of lipoprotein(a) as a way of mimicking a randomized controlled trial. This approach has previously been undertaken for other biomarkers, including LDL-cholesterol. We found that having 10mg/dL lower genetically-predicted concentration of lipoprotein(a) was associated with a 5.8% reduction in coronary heart disease risk. However, associations between genetically-predicted LDL-cholesterol and coronary heart disease risk are quantitatively much stronger than the proportional effect of LDL-cholesterol lowering on coronary heart disease risk as estimated by statin trials. This is because differences in genetic variants reflect lifelong changes in LDL-cholesterol, whereas statin trials only lower LDL-cholesterol for a few years. Hence, using the ratio between the genetic and trial estimates for LDL-cholesterol, we estimate that lowering lipoprotein(a) by 10mg/dL in a short-term clinical trial would only reduce coronary heart disease risk by 2.7%. To obtain the same reduction in coronary heart disease risk of around 20% as observed in statin trials, lipoprotein(a) would have to be lowered by around 100mg/dL. This explains why previous trials of less specific and less potent lipoprotein(a)-lowering drugs have failed to demonstrate benefit. (more…)
Author Interviews, Environmental Risks, Pediatrics, PLoS, Toxin Research / 19.06.2018

MedicalResearch.com Interview with: Cheryl Rosenfeld PhD DVS Professor of biomedical sciences in the College of Veterinary Medicine investigator in the Bond Life Sciences Center, and research faculty member for the Thompson Center for Autism and Neurobehavioral Disorders University of Missouri MedicalResearch.com: What is the background for this study? What are the main findings? Response: My laboratory has been examining the effects of developmental exposure to the endocrine disrupting chemical (EDC), bisphenol A (BPA) on later neurobehavioral responses in a variety of rodent models, including California mice. This species is unique in that both parents rear the pups and they have monogamous social structure, similar to most human societies. We had previously found that developmental exposure to BPA or another EDC, ethinyl estradiol (EE), disrupted later maternal and paternal care by F1 offspringto their F2 pups. Rodent pups use vocalizations both in the range of human hearing (20,000 hertz or below) and outside of the range of human hearing (20,000 hertz) to communicate with each other and their parents, and for the latter, such communications serve as a trigger to provide additional parental care in the form of nutrition or warmth to the pups. Thus, in the current studies we sought to determine if exposure of the grandparents to BPA or EE could lead to disruptions in their grandoffspring (F2 generation) pup communications that might then at least partially account for the parental neglect of their F1 parents. We found that early on female BPA pups took longer to call to their parents but later during the neonatal period they vocalized more than pups whose grandparents were not exposed to either chemical. Such vocalization changes could be due to multigenerational exposure to BPA and/or indicate that the pups are perceiving and responding to the reduced parental care and attempting but failing to signal to their F1 parents that they need more attention. (more…)
Author Interviews, Cancer Research, Genetic Research, Nature, Prostate Cancer / 13.06.2018

MedicalResearch.com Interview with: Fredrick R. Schumacher, PhD, MPH. Associate Professor, Department of Population & Quantitative Health Sciences Case Western Reserve University Cleveland MedicalResearch.com: What is the background for this study? What are the main findings?  Response: Our study examines the genetic underpinnings of prostate cancer initiation using technology to test variants across the genome. Our study focused on men of European ancestry and included over 80,000 men with prostate cancer and 60,000 men without disease. We discovered 63 novel genetic variants associated with prostate cancer risk, which increases our knowledge of prostate cancer genetic risk factors by more than 60%. A genetic risk score created from the combination of 163 new and known prostate cancer risk variants revealed men with the highest genetic risk score are nearly seven times more likely to develop disease compared to the average man. Additionally, men with the lowest genetic risk score have a 85% risk reduction of developing prostate cancer compared to the average. Lastly, these new discoveries uncover several biological mechanisms involved in the initiation of prostate cancer. (more…)