Author Interviews, Dermatology, Genetic Research / 04.12.2017

MedicalReseaerch.com Interview with: Alicia R. Martin PhD, Postdoc Department of Genetics Stanford University Department of Medicine, Massachusetts General Hospital and Harvard Medical School Stanley Center for Psychiatric Research, Broad Institute, Cambridge, MA and Brenna M. Henn, Phd, Assistant Professor Department of Ecology and Evolution SUNY Stony Brook, NY  MedicalResearch.com: What is the background for this study? What are the main findings? Response: Skin pigmentation varies more in Africa than in any other continent, and yet genetic studies of this and other traits are massively underrepresented there. Previous Eurasian study biases have instead focused on populations that vary less and have fewer variants contributing to baseline skin color. In our study, we compiled quantitative skin color measurements from a large, globally diverse set of individuals and populations to show that pigmentation varies more closer to the equator than in high latitude populations. We focused on the ‡Khomani San and Nama populations from South Africa, which diverged early along the modern human lineage from other populations and have lighter skin than equatorial Africans. We showed that skin pigmentation is roughly 100% heritable, but that previously identified genes make up a tiny fraction (~10%) of the variation present in these populations. We identified both known and new genes contributing to this variability. (more…)
Author Interviews, Genetic Research, Heart Disease, JAMA, Lipids / 15.11.2017

MedicalResearch.com Interview with: Hao Yu Chen, MSc Department of Medicine McGill University Montreal, Quebec, Canada Senior author: George Thanassoulis, MD, MSc MedicalResearch.com: What is the background for this study? Response: Aortic stenosis, a narrowing of the main valve of the heart, is the most common type of valve disease in the US. Present in more than 2.5 million individuals in North America, aortic stenosis can lead to heart failure and death. However, there is little known about the causes of aortic stenosis and how it should be treated. Previously, we have demonstrated that variants of the gene LPA are associated with the development of aortic stenosis. A better understanding of how this region contributes to aortic stenosis could identify higher-risk individuals and inform the development of new medical therapies for aortic stenosis.  (more…)
Author Interviews, Autism, Genetic Research, Nature / 12.11.2017

MedicalResearch.com Interview with: Woo-Yang Kim, Ph.D Associate Professor Department of Developmental Neuroscience Munroe-Meyer Institute University of Nebraska Medical Center Omaha, NE 68198-5960 MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Autism impairs the ability of individuals to communicate and interact with others. About 75 percent of individuals with autism also have intellectual disability, which is characterized by significant limitations in cognitive functions and adaptive behaviors. While autism and intellectual disability are currently defined using behavioral criteria, little is known about the neuropathogenesis of these conditions. Recent genetic studies have reported that haploinsufficiency of ARID1B causes autism and intellectual disability. However, the neurobiological function of ARID1B during brain development is unknown. Our study investigated the neurobiological role of the gene in brain development. Using genetically-modified mice, we found that Arid1b haploinsufficiency leads to an excitation-inhibition imbalance by reducing the number of GABAergic interneurons in the cerebral cortex. Furthermore, we showed that treatment with a GABAA-receptor positive allosteric modulator rescues ASD-like behavior and cognitive dysfunction in Arid1b-haploinsufficient mice, suggesting an association between lower numbers of GABAergic interneurons and behavioral outcomes. Our findings suggest a pathogenic mechanism for Autism Spectrum Disorder and intellectual disability. (more…)
Author Interviews, Dental Research, Genetic Research / 07.11.2017

MedicalResearch.com Interview with: “Dental Mold_002” by Ano Lobb is licensed under CC BY 2.0Alexandre R. Vieira, DDS. MS, PhD Professor, Director of Clinical Research,  Director of Student Research Department of Oral Biology Center for Craniofacial and Dental Genetics Department of Pediatric Dentistry School of Dental Medicine Department of Human Genetics Graduate School of Public Health Clinical and Translational Sciences Institute University of Pittsburgh  MedicalResearch.com: What is the background for this study? What are the main findings? Response: One aspect is the dilemma between continuing to use dental amalgams and the perception that composite resins are not as durable. We show that composite resin restorations can perform similarly to dental amalgams for the first 5 years. But the most remarkable is that composite resin failures may be related to certain individual risk factors, such as genetic variation. (more…)
Author Interviews, Mental Health Research, Nature / 30.10.2017

MedicalResearch.com Interview with: Hyun Ji Noh PhD Computational Scientist, Medical and Population Genetics Broad Institute of MIT and Harvard MedicalResearch.com: What is the background for this study? What are the main findings? Response: Obsessive-compulsive disorder (OCD) is a debilitating neuropsychiatric disorder, characterized by intrusive thoughts and repetitive behaviors. OCD is estimated to affect roughly 80 million people worldwide, but its neurobiology remains poorly understood. To understand the disorder’s underpinnings, we searched for genetic mutations that are associated with OCD. For this, we first identified 608 genes that were most likely to be important  in OCD - some that have previously been identified in OCD-like behaviors in dogs and mice, and others in human autism, which also involves repetitive behaviors. We compared these genes in 592 people with OCD and 560 people without OCD, and found that 4 of these genes were significantly different between people with and without OCD: NRXN1, HTR2A, CTTNBP2 and REEP3. All of these four genes have important functions in the brain. Specifically, we found that the variants in NRXN1 are likely to change its ability to bind other synaptic proteins. Synaptic proteins link neurons together, and are critical for transmitting signals through the brain. We also found that the variants in CTTNBP2 and REEP3 don’t actually change the proteins made by these genes, but instead probably affect gene regulation (for example, how much of the protein is made). These ‘regulatory’ variants disrupt the binding of transcription factors (proteins that regulate expression of genes in the body) near the gene. (more…)
Author Interviews, Genetic Research, PLoS / 07.10.2017

MedicalResearch.com Interview with: Colin Sharpe School of Biology Institute of Biomolecular and Biomedical Science School of Biological Sciences University of Portsmouth Portsmouth, United Kingdom  MedicalResearch.com: What is the background for this study? What are the main findings? Response: We have long been fascinated by the question of what underpins the increasing complexity of multicellular animals. In a recent publication we looked at changes to the diversity of the NCoR family corepressors (NCoRs) across the Deuterostomes and found an increase in diversity from sea urchins to humans (1). This is due to gene duplication, an increase in alternative splicing and the encorporation of more protein motifs and domains. In this study we devised a measure of functional diversity based on these three factors and calculated this value for over 12000 genes involved in transcription in nine species from the nematode worm to humans. Orthologues whose increase in diversity correlated with the increase in complexity of these animals were then selected and we looked for common features and interactions between the selected genes. We found that proteins that regulate the dynamic organisation of chromatin were significantly enriched within the selection. (more…)
Author Interviews, Columbia, Genetic Research / 29.09.2017

MedicalResearch.com Interview with: Carlos Eduardo G. Amorim PhD Columbia University Department of Systems Biology Irving Cancer Research Center  MedicalResearch.com: What is the background for this study? Response: More generally, we were interested in understanding the determinants of the frequencies of mutations that cause disease in humans. More specially, we wanted to test if a long-standing theory in population genetics (namely mutation-selection balance) was a good explanation for the observed frequencies of disease mutations in humans. (more…)
Author Interviews, Autism, Genetic Research, JAMA / 27.09.2017

MedicalResearch.com Interview with: Sven Sandin, PhD Assistant Professor Department of Psychiatry Icahn School of Medicine at Mount Sinai New York, NY 10029  MedicalResearch.com: What is the background for this study? What are the main findings? Response: In 2014, we estimated the heritability of autism to be approximately 50%. Motivating us then was the lack of studies in autism heritability using population based and the findings from a twin-study in California finding the heritability to be substantially lower than the 80-90% estimated in previous studies. Since then continued efforts working with the questions on heritability and environmental factors for autism we found differences between different methods and different samples. When we went back to our previous data we found the heritability of autism to be higher than previously estimated. We found that our previous result was due to a methodological artifact where the adjustment for differences in follow-up used in that manuscript underestimated the heritability. Using methods used in other heritability studies the heritability is now estimated to 84%. Importantly, as previously concluded, there is no support for any ‘shared environmental factors’ in the etiology of autism, e.g. environmental factors shared between two siblings. (more…)
Author Interviews, Prostate Cancer, Radiation Therapy / 26.09.2017

MedicalResearch.com Interview with: Dr. Shuang George Zhao, MD House Officer, Radiation Oncology University Hospital Ann Arbor, MI 48109 MedicalResearch.com: What is the background for this study? Response: Targeting cancer through the immune system has been a longstanding goal of cancer research, and with recent advances in immunotherapy, it is now a reality. However, the role of immunotherapy in prostate cancer is still being defined. Sipuleucel-T was the first FDA approved immunotherapy in prostate cancer, and is a personalized cellular therapy that has been shown to prolong survival in patients with metastatic prostate cancer. On the other hand, two recent phase III randomized trials looking at ipilimumab, a CTLA-4 checkpoint inhibitor in metastatic prostate cancer have both been negative for their primary endpoint of OS. Interestingly, there was a PSA response, suggesting that there may be some therapeutic effect in a subset of patients. Therefore, understanding the immune infiltrate is likely critical to selecting patients and therapeutic strategies utilizing the immune system. Unfortunately, it is difficult and laborious to histologically assess immune infiltrate directly. Therefore, we used existing high throughput transcriptomic data with new computational methods in order to more fully characterize the immune landscape of localized prostate cancer. (more…)
Author Interviews, Genetic Research, Melanoma / 08.09.2017

MedicalResearch.com Interview with: Rutao Cui, MD/PhD Professor Vice Chair for Laboratory Administration Director, Laboratory of Melanoma Biology Department of Pharmacology and Experimental Therapeutics Professor of Dermatology Boston University Boston, Mass 02118 MedicalResearch.com: What is the background for this study? Response: Red-headed people are making up to 1~2% of the world’s population. They carry “red hair color” variants of MC1R (MC1R-RHC) which are responsible for their characteristic features, including red hair, pale skin, freckles and poor tanning ability. MC1R-RHC also increases risk of melanoma, the deadliest form of skin cancer. People without red hair but with a single copy of MC1R-RHC also have an increased melanoma risk, who may make more than 50% of the northern European population. It is unknown why redheads are more prone to melanoma, and whether the activity of red hair color variants could be restored for therapeutic benefits. (more…)
Author Interviews, Genetic Research, PLoS / 07.09.2017

MedicalResearch.com Interview with: Hakhamanesh Mostafavi, MS PhD student Department of Biological Sciences Columbia University  MedicalResearch.com: What is the background for this study? Response: We know very little about the genetic variants that underlie adaptation in humans. This is in part because we have mostly been limited to methods that search for footprints of ancient selection (that has acted for over thousands to millions of years) in the genomes of present-day humans; so by design are indirect and make strong assumptions about the nature of selection. These days, thanks to advances in genomic technologies, genetic data for large numbers of people is being collected, mostly for biomedical purposes. Accompanied by information on survival and reproductive success of these individuals, such large datasets provide unprecedented opportunities for more direct ways to study adaptation in humans. In this work, we introduced an approach to directly observe natural selection ongoing in humans. The approach consists in searching for mutations that change in frequency with the age of the individuals that carry them, and so are associated with survival. We applied it to around 210,000 individuals from two large US and UK datasets. (more…)
Alzheimer's - Dementia, Author Interviews, Gender Differences, Genetic Research, JAMA / 29.08.2017

MedicalResearch.com Interview with: Arthur W. Toga PhD Provost Professor of Ophthalmology, Neurology, Psychiatry and The Behavioral Sciences, Radiology and Engineering Ghada Irani Chair in Neuroscience Director, USC Mark and Mary Stevens Neuroimaging and informatics institute USC Institute for Neuroimaging and Informatics Keck School of Medicine of USC University of Southern California Los Angeles, CA  90032  MedicalResearch.com: What is the background for this study? What are the main findings? Response: The ε4 allele of the Apolipoprotein E (APOE) gene is the main genetic risk factor for late-onset Alzheimer's disease.  This study reexamines and corrects the sex-dependent risks that white men and women with one copy of the ε4 allele face for developing Alzheimer's disease using a very large data set of 57,979 North Americans and Europeans from the Global Alzheimer's Association Interactive Network (GAAIN). The study results show that these men and women between the ages of 55 and 85 have the same odds of developing Alzheimer's disease, with the exception that women face significantly higher risks than men between the ages of 65 and 75.  Further, these women showed increased risk over men between the ages of 55 and 70 for mild cognitive impairment (MCI), which is often a transitional phase to dementia. (more…)
AHA Journals, Author Interviews, Genetic Research, Heart Disease, Lipids, UCLA / 28.08.2017

MedicalResearch.com Interview with: Tamer Sallam, MD PhD Assistant Professor of Medicine Co-Director UCLA Center for Lipid Management Lauren B. Leichtman and Arthur E. Levine CDF Investigator Assistant Director, STAR Program Division of Cardiology, Department of Medicine David Geffen School of Medicine at UCLA Los Angeles, California 90095-1679 MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study is extension of our previous work published in Nature showing that a gene we named LeXis (Liver expressed LXR induced sequence) plays an important role in controlling cholesterol levels. What is unique about  LeXis is that it belongs to a group of newly recognized mediators known as long noncoding RNAs. These fascinating factors were largely thought to be unimportant and in fact referred to as “junk DNA” prior the human genome project but multiple lines of evidence suggest that they can be critical players in health and in disease. In this study we tested whether we can use  LeXis “gene therapy”  to lower cholesterol and  heart disease risk. This type of approach is currently approved or in testing for about 80 human diseases. Our finding was that a single injection of LeXis compared with control significantly  reduced heart disease burden in mouse subjects. Although the effect size was moderate we specifically used a model that mimics a very challenging to treat human condition known as familial hypercholesterolemia..Familial hypercholesterolemia is one of the most common genetic disorders affecting up to 2 million Americans and characterized by 20 fold  fold increase risk of early heart attacks and often suboptimal response to currently available treatments. (more…)
Author Interviews, Genetic Research, JAMA, Pancreatic, Surgical Research / 25.08.2017

MedicalResearch.com Interview with: Nancy You, MD, MHSc, FACS Department of Surgical Oncology The University of Texas MD Anderson Cancer Center Houston  MedicalResearch.com: What is the background for this study? What are the main findings? Response: This study was motivated by the emerging promise of precision medicine and the emerging evidence that immunotherapy may have phenomenal efficacy in particular molecular subtypes of cancers.  This specific molecular subtype shows deficiency in DNA mismatch repair mechanisms and therefore is thought to be more immunogenic.  DNA mismatch repair deficiency can arise from germline defects such as in the case of patients with Lynch Syndrome, an inherited cancer syndrome, or from epigenetic inactivation DNA mismatch repair genes. Overall, pancreas cancer has seen limited success with conventional chemotherapy.  In our study, we demonstrated that there is a particular molecular subtype of pancreas cancer that is characterized by defect in DNA mismatch repair genes and by microsatelie instability that has a different prognosis than other pancreas cancers.  This subtype of pancreas cancer is suspected to also respond to immunotherapy. (more…)
Author Interviews, Genetic Research, Nature / 29.07.2017

MedicalResearch.com Interview with: Dr. Zoltán Kutalik, PhD Group Leader Swiss Institute of Bioinformatics Assistant professor at the Institute of Social and Preventive Medicine MedicalResearch.com: What is the background for this study? What are the main findings? Response: Why do some of us live longer than others? While the environment in which we live – including our socio-economic status or the food we eat – plays the biggest part, about 20 to 30% of the variation in human lifespan comes down to our genome. Changes in particular locations in our DNA sequence, such as single-nucleotide polymorphisms (SNPs), could therefore hold some of the keys to our longevity. Until now, the most comprehensive studies had found only two hits in the genome. (more…)
Author Interviews, Eating Disorders, Genetic Research / 24.06.2017

MedicalResearch.com Interview with: Camron D. Bryant Ph.D Laboratory of Addiction Genetics, Department of Pharmacology and Experimental Therapeutics and Department of Psychiatry Boston University, Boston, MA MedicalResearch.com: What is the background for this study? What are the main findings? Response: We previously used genome-wide linkage analysis, fine mapping, gene validation, and pharmacological targeting to identify a negative regulatory role for the gene casein kinase 1-epsilon (Csnk1e) in behavioral sensitivity to drugs of abuse, including psychostimulants and opioids. Parallel human candidate genetic association studies identified an association between multiple genetic variants in CSNK1E with heroin addiction in multiple populations. Drug addiction is a multi-stage process that begins with the initial acute subjective and physiological responses that can progress to chronic administration, tolerance, and withdrawal. The recovery process begins with abstinence from drug taking but can quickly be derailed by relapse to drug taking behavior. Preclinical pharmacological studies also support a role for CSNK1E in reinstatement of opioid self-administration and relapse to alcohol drinking. Despite the evidence that disruption of Csnk1e gene and protein function can affect various behaviors associated with drug and alcohol addiction, it is unclear what stage of the addiction process these genetic and pharmacological manipulations modulate. In this study, we show that disruption of the Csnk1e gene resulted in an enhancement of the rewarding properties of the highly potent and addictive opioid, fentanyl.  Unexpectedly, we also discovered that disruption of Csnk1e also enhanced binge eating – but only in female mice. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research / 22.06.2017

MedicalResearch.com Interview with: Mikko Hiltunen, PhD Professor of Tissue and Cell Biology University of Eastern Finland School of Medicine, Institute of Biomedicine Kuopio,  Finland  MedicalResearch.com: What is the background for this study? What are the main findings? Response:  We wanted to assess among the population-based METSIM (METabolic Syndrome In Men) cohort whether protective variant in APP gene (APP A673T) affects the beta-amyloid levels in plasma. The rationale behind this was that previous genetic studies have discovered that the APP A673T variant decreases the risk of having Alzheimer’s disease (AD). However, the protective functional outcome measures related to this variant were lacking and thus we anticipated that the elucidation of plasma samples in terms of beta-amyloid levels would provide the much needed link between APP A673T variant and potential protective functions. (more…)
Author Interviews, Cancer Research, Genetic Research / 22.06.2017

MedicalResearch.com Interview with: Antonis Antoniou PhD Reader in Cancer Risk Prediction Academic Course Director MPhil in Epidemiology Centre for Cancer Genetic Epidemiology Department of Public Health and Primary Care Strangeways Research Laboratory Cambridge University of Cambridge MedicalResearch.com: What is the background for this study? What are the main findings? Response: Several studies demonstrated that women with genetic faults in the BRCA1 and BRCA2 genes are at increased risk of developing breast and ovarian cancer. Having accurate age-specific cancer risk estimates for women with mutations is essential for their optimal clinical management. Most studies to date that estimated cancer risks for BRCA1 and BRCA2 mutation carriers have been "retrospective", in other words they look at what happened in the past. Estimates from such studies are prone to biases because they rely on the experience of women who have already developed cancer and on self-reported cancer family history information on relatives - which may have inaccuracies. The ideal epidemiological study design for estimating cancer risks are prospective studies.  In prospective studies, healthy women with genetic faults are followed over time and overcome these potential biases. However, to date, published  prospective studies have been very small. In the present study we used data from a prospective cohort of women with BRCA1 and BRCA2 mutations who were recruited from 1997 to 2011 and were followed over time. The study included almost 10,000 women who were included in the analyses, and was made possible through collaborations between scientists from Europe, North America and Australia.  The prospective study design explains why it has taken 20 years of hard work to get these results. Most importantly, it took an enormous long-term contribution and commitment from the women themselves to allow the scientists to be able to assemble this dataset. Here, we were able to estimate more precisely the breast and ovarian cancer risks for women with faults in BRCA1 and BRCA2.  These risk estimates will provide more confidence in the counseling and clinical management of women with faults in the BRCA1 and BRCA2  genes. A novel finding in this study is that breast cancer risk for women with faults in BRCA1 and BRCA2  increases rapidly at a young age then remains at a constant high level for the rest of their lives. It peaks in the 40’s for BRCA1 mutation carriers and in the 50’s for BRCA2 carriers, but  carriers of mutations in both genes  are at about the same high risk in later life. This is important information to inform the clinical management of older mutation carriers. This study also shows clearly that for women with a mutation, there are other factors that are important in modifying the breast cancer risk. The study has demonstrated that the extent of the woman’ family history of cancer and the exact place on the gene where her mutation is located are very important in determining the actual risk. (more…)
Author Interviews, Genetic Research, Nature, Scripps / 21.06.2017

MedicalResearch.com Interview with: Michael Farzan PhD Co-chair and Professor Department of Immunology and Microbiology Florida Campus The Scripps Research Institute Jupiter, Florida MedicalResearch.com: What is the background for this study? What are the main findings? Response: CRISPR is system for immune protection of bacteria.  It has now been widely adopted for use in editing mammalian cells.  The most commonly used CRISPR effector protein is Cas9.  Cas9 binds a guide RNA to recognize a DNA target, for example an incoming virus infecting a bacterium, or a gene in a human chromosome.  In bacteria, Cas9 requires a second protein to clear the guide RNA from a longer "CRISPR array", basically a string of guide RNAs. We have been studying a CRISPR effector protein related to Cas9 called Cpf1.  In bacteria it was know that, unlike Cas9, Cpf1 could cleave a CRISPR array by itself, without assistance from a second protein.  We knew that if it could do the same thing in human cells, it would help to simplify a number of gene-editing applications.  We were able to show that Cas9 could indeed excise multiple guide RNAs from a single message RNA in human cells.  We further showed that this approach was more efficient than the previous ways that guide RNAs were generated for gene editing, even more so when multiple guide RNAs were needed. (more…)
Author Interviews, Genetic Research, Lifestyle & Health / 21.06.2017

MedicalResearch.com Interview with: Ivana Buric Brain, Belief, and Behaviour Lab Centre for Psychology, Behaviour, and Achievement, Faculty of Health and Life Sciences Coventry University, Coventry, United Kingdom Donders Institute for Brain, Cognition and Behaviour Radboud University, Nijmegen, Netherlands MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Genes that we inherited can change their activity - the​y can be active and produce proteins, but they can also stop producing proteins and remain silent. We are now beginning to understand what aspects of our environment affect the activity of which genes. In this study, we analysed all the existing studies that examined the effects of mind-body interventions on the expression of our genes and found that mind-body techniques reduce the activity of genes that produce inflammatory proteins. This pattern was found in all studies despite the fact that they vary in the amount of physical activity: Tai Chi, yoga, breathing techniques and different types of meditation. We believe that this effect is observed due to reduced stress. When we experience something stressful, the brain regions associated with pain get activated and send that signal further to sypmathetic nervous system that produces epinephrine and norepinefrine, and activates nuclear factor kappa B - a molecule that travels to and activated the genes that produce inflammatory proteins. When we do yoga or meditation, we learn to perceive situations differently and consequently experience less stress, which then prevents the production of inflammatory proteins. (more…)
Author Interviews, Endocrinology, Genetic Research, NYU / 19.06.2017

MedicalResearch.com Interview with: Constantine A. Stratakis, MD, DMSci Section on Endocrinology and Genetics Eunice Kennedy Shriver National Institute of Child Health and Human Development National Institutes of Health, Bethesda  MedicalResearch.com: What is the background for this study? Response: The pituitary and adrenal glands operate on a kind of feedback loop.  In response to stress, the pituitary release ACTH (Adrenocorticotropic hormone), which signals the adrenal glands to release cortisol.  Rising cortisol levels then act on the pituitary, to shut down ACTH production. In a previous study, Jacque Drouin of the Institute for Clinical Research in Montreal and colleagues had determined that the CABLES1 protein was a key player in this feedback mechanism, switching off pituitary cell division in cultures exposed to cortisol. Since this feedback mechanism appears to be impaired in many corticotropinomas, we investigated the presence of Cables1 gene mutations and copy number variations in a large group of patients with Cushing’s disease. (more…)
Author Interviews, Genetic Research, Nutrition, Omega-3 Fatty Acids / 16.06.2017

MedicalResearch.com Interview with: Kaixiong (Calvin) Ye, PhD Post-doctoral Associate Dept. of Biological Statistics & Computational Biology Cornell University thaca, NY MedicalResearch.com: What is the background for this study? Response: Omega-6 and omega-3 fatty acids are critical for human brain development, cognitive function, immune response, and cardiovascular health. Physiologically active forms of omega-6 and omega-3 fatty acids, such as AA, EPA, and DHA, are readily available in meat and seafood, but are absent in most plant-based foods (e.g. fruits and vegetables). Instead, plant-based foods contain two precursor fatty acids, LA and ALA, which could be metabolized in our body and converted into physiologically active forms. Fatty acid desaturase (FADS) genes encode key enzymes for this biosynthesis. We hypothesized that genetic variations in FADS genes that enhance the biosynthesis efficiency were adaptive to plant-based diets in traditional farming populations and thus became more frequent over time. Our study compiled a huge data set of genetic information (DNA) from both present-day and ancient individuals. For the first time, we examined the action of natural selection on humans for the past 30,000 years in Europe. (more…)
Author Interviews, Genetic Research, Pediatrics / 14.06.2017

MedicalResearch.com Interview with: Charlotte Cecil, PhD ESRC FRL Fellow Edward Barker, PhD Lab Director, DEVELOPMENTAL PSYCHOPATHOLOGY LAB Department of Psychology Institute of Psychiatry, Psychology& Neuroscience King's College London MedicalResearch.com: What is the background for this study? What are the main findings? Response: Conduct problems (CP) are the most common reason for child treatment referral in the UK, costing an estimated £22 billion per year. Children with CP engage in a range of aggressive and antisocial behaviours (e.g. fighting, stealing, lying), that affect their ability to follow rules and adapt to society, do well in school, and form healthy relationships. Those who do not receive treatment are also at increased risk for many negative outcomes in adulthood, including lower job prospects and earnings, more contact with the police and a lower quality of life. Therefore, it is important to understand how CP develop in the first place, in order to create more effective prevention and intervention strategies. Studies have found that children who develop conduct problems before the age of 10 (early-onset CP) are at greatest risk for poor outcomes across the lifespan. Compared to other children, those showing early-onset CP tend to have experienced more adversity in early life (e.g. prenatal stress, poverty) as well as having more genetic risk. However, little is known about about how genetic factors interact with environmental influences - especially during foetal development - to increase the risk for early-onset conduct problems. (more…)
Author Interviews, Dermatology, Genetic Research, Yale / 05.06.2017

MedicalResearch.com Interview with: Keith Adam Choate, MD, PhD, FAAD Associate Professor of Dermatology, Genetics and Pathology Director of Research, Dermatology Yale University School of Medicine New Haven, CT MedicalResearch.com: What is the background for this study? What are the main findings? Response:  Over the last 10 years, we have systematically been examining patients with ichthyosis to identify new genetic causes of this group of disorders.  We found that autosomal recessive mutations in KDSR cause ichthyosis and that the resulting skin disease is effectively treated with isotretinoin. (more…)
Alzheimer's - Dementia, Author Interviews, Genetic Research, Mental Health Research / 23.05.2017

MedicalResearch.com Interview with: Auriel Willette, M.S., Ph.D. Assistant Professor Departments of Food Science and Human Nutrition and Psychology Iowa State University MedicalResearch.com: What is the background for this study? What are the main findings? Response: Translocase of Outer Mitochondrial Membrane 40 (TOMM40) is a gene that regulates the width of the outer mitochondrial pore, facilitating the transport of ribosomal pre-proteins into the inner mitochondrial matrix for translational modification into functional proteins. In 2010, Dr. Allen Roses, who discovered the Apolipoprotein E (APOE) gene, Dr. Michael Lutz, and other colleagues found that a variation in poly-T length at locus rs10524523 ('523) within intron 6 predicted Alzheimer's disease onset. Specifically, a "long" versus "short" poly-T length was related to earlier age of onset by 8 years. However, several multi-cohort studies either failed to replicate the findings or found the opposite relationship, where a "long" or "very long" poly-T length was related to later age of onset. The literature has remained mixed to this day. We were interested in testing factors that might change the relationship between TOMM40 and both cognitive decline and risk for having Alzheimer's disease. It is known that a family history (FH) of Alzheimer's disease has been associated with mitochondrial dysfunction. We reasoned, then, that FH may interact with TOMM40 to modulate how it was related to our outcomes of interest. We investigated this hypothesis in two separate cohorts: the Wisconsin Registry for Alzheimer's Prevention (WRAP), a late middle-aged cohort, and the Alzheimer's Disease Neuroimaging Initiative (ADNI), a well-characterized sample of aged participants from across the Alzheimer's spectrum. (more…)
Author Interviews, Biomarkers, Genetic Research, Personalized Medicine / 15.05.2017

MedicalResearch.com Interview with: 3D SignaturesJason Flowerday, CEO Director of 3D Signatures  MedicalResearch.com: What is the background for 3D Signatures? Response: 3D Signatures, and its clinical lab tests, which incorporate its proprietary TeloViewTM software analytics, is the culmination of over 20 years of ground-breaking research conducted by Dr. Sabine Mai and her colleagues. It is the only technology in the world that quantifies genomic instability, which is the hallmark of cancer and other proliferative diseases at the whole-cell level. By measuring the degree of genomic instability from different tissues, TeloViewTM has produced clinically actionable distinctions in the stage of disease, rate of progression of disease, drug efficacy, and drug toxicity. The technology is well developed and supported by 22 clinical studies on over 2,000 patients on 13 different cancers including Alzheimer’s disease. The results have been exceptional and represent a universal biomarker platform across all disease areas that the company has investigated to date. (more…)
Author Interviews, Genetic Research, Ophthalmology / 15.05.2017

MedicalResearch.com Interview with: Zheng-Rong Lu, Ph.D. M. Frank Rudy and Margaret Domiter Rudy Professor of Biomedical Engineering Department of Biomedical Engineering Case Western Reserve University Cleveland, OH 44106 MedicalResearch.com: What is the background for this study? What are the main findings? Response: Genetic vision disorders are a major cause of severe vision loss and blindness, especially in children and young adults. Currently, there are no approved therapies to treat these types of disorders. This study focused on one such disease known as Leber’s congenital amaurosis type 2 (LCA2). Patients with LCA2 are born with some degree of vision loss, and are often legally blind by early adulthood. LCA2 is a recessive disease caused by a mutation in one of the genes responsible for visual processing. LCA2 is a good candidate for gene therapy, and clinical trials underway to test viral vectors that deliver a healthy copy of the mutated gene into the eye have demonstrated considerable therapeutic efficacy. These trials have validated the feasibility of gene therapy to treat this disease, however viral vectors are limited by potential safety issues, complex preparation methods, and limitations on the size of genes that can be delivered. In this study, we successfully treated LCA2 in mice for 120 days by delivering the gene responsible for LCA2 in a synthetic lipid nanoparticle instead of a viral vector. Our delivery system, called ECO, specifically targets the cells in the retinal pigmented epithelium, where the mutation behind LCA2 occurs. Our nanoparticle delivery system is easy to produce, safe, and has unlimited cargo capacity. Most important, our nanoparticle gene delivery system is a platform that can be used to deliver any gene into the retina, opening the door for safe and effective gene therapy for any genetic vision disorder. (more…)
Abuse and Neglect, Genetic Research, Technology / 03.05.2017

MedicalResearch.com Interview with: Chance York, Ph.D. Assistant Professor of Mass Communication Kent State University MedicalResearch.com: What is the background for this study? What are the main findings? Response: This research used twin study survey data from the Midlife in the United States (MIDUS) to investigate the relative influence of genetics and environment on social media use. While the research cannot directly examine the gene-level influence on social media behavior, I was able to leverage known levels of genetic relatedness between identical and fraternal twins to suss out how much genetic traits and environmental factors impact frequency of using social media with some help from the Buzzoid boys. The results showed that between one- and two-thirds of variance in social media use is explained by genes, while environmental factors (parental socialization, peers, work, school, individual characteristics, etc.) explained the rest. In other words, this very specific communication behavior—social media use—is partially guided by our genetic makeup. (more…)
Author Interviews, Biomarkers, Genetic Research, Lung Cancer / 25.04.2017

MedicalResearch.com Interview with: Hestia Mellert, PhD Director, Molecular Product Development Biodesix: Making Medicine Personal Boulder, CO MedicalResearch.com: What is the background for this study? What are the main findings? Response: Identifying specific genetic mutations in non-small cell lung cancer patients helps clinicians choose the best treatment options; specific therapies that target mutations can improve patient outcomes, including reducing the risk of death or lessening the severity of the disease. However, nearly 80% of cancer patients do not have genetic mutation results available at initial oncology consultation; up to 25% of patients begin treatment before receiving their results. These factors hinder physicians’ ability to pursue optimal treatment strategies. This study found that a blood-based assay, the GeneStrat test, provides results in 72 hours for 94% of patients, which expands testing options, and supports faster treatment decisions by physicians. (more…)
Addiction, Genetic Research, Opiods / 24.04.2017

MedicalResearch.com Interview with: Maneesh Sharma, M.D Director of Pain Medicine MedStar Good Samaritan Hospital Medical Director of the Interventional Pain Institute Baltimore, Maryland MedicalResearch.com: What is the background for this study? Response: Opioid abuse in chronic pain patients is a major public health issue, with rapidly increasing addiction rates and deaths from unintentional overdose more than quadrupling since 1999. Just in the last year alone according to the CDC, synthetic opioid deaths have increased 72%. As a practicing interventional pain specialist, I am confronted with the challenge of assessing patient risk for opioids as I evaluate multi-modal approaches to effective pain management. Existing tools are inadequate, as they either rely on a urine toxicology test to evaluate a patient’s current potential substance abuse as a predictor of future abuse, or on a patient’s honesty to fill out a questionnaire. We know that many patients who are not currently abusing illicit drugs or misusing prescription medications can develop prescription opioid tolerance, dependence, or abuse—especially with prolonged opioid therapy. Furthermore, we know that patients who are looking to abuse medications or divert those prescriptions will obviously lie on questionnaires. (more…)