Children with Birth and Chromosomal Defects More Likely to Develop Cancer

MedicalResearch.com Interview with:

Philip J. Lupo, PhD, MPH Co-Director, Childhood Cancer Epidemiology and Prevention Program, Texas Children's Cancer Center Associate Professor, Department of Pediatrics Section of Hematology-Oncology, Member, Dan L. Duncan Comprehensive Cancer Center Baylor College of Medicine Adjunct Associate Professor, Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences University of Texas School of Public Health

Dr. Lupo

Philip J. Lupo, PhD, MPH
Co-Director, Childhood Cancer Epidemiology and Prevention Program, Texas Children’s Cancer Center
Associate Professor, Department of Pediatrics
Section of Hematology-Oncology,
Member, Dan L. Duncan Comprehensive Cancer Center
Baylor College of Medicine
Adjunct Associate Professor, Human Genetics Center, Division of Epidemiology, Human Genetics and Environmental Sciences
University of Texas School of Public Health
 

MedicalResearch.com: What is the background for this study?  

Response: While cancer risk in children with certain chromosomal defects like Down syndrome is well established, much less is known for children with birth defects where there is no known genetic cause, sometimes called non-chromosomal defects. Non-chromosomal defects, as a group, affect more children, but one of the primary challenges of understanding risk among these children is that limited sample sizes make studying specific defects, like spina bifida, more difficult.

Because of that, we gathered data from birth, birth defect, and cancer registries across Texas, Arkansas, Michigan, and North Carolina to generate a birth cohort of more than 10 million children born between 1992 and 2013. We looked at diagnoses of cancer until 18 years of age to determine differences in cancer risk between those with and without birth defects.

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World Trade Center 9/11 Dust: Altered Gene Expression Links Exposure to Prostate Cancer Risk

MedicalResearch.com Interview with:

Emanuela Taioli, MD, PhD, Director of the Institute for Translational Epidemiology Icahn School of Medicine at Mount Sinai Asociate director for Population Science Tisch Cancer Institute

Dr. Taioli

Emanuela Taioli, MD, PhD,
Director of the Institute for Translational Epidemiology
Icahn School of Medicine at Mount Sinai
Asociate director for Population Science
Tisch Cancer Institute 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: An excess incidence of prostate cancer has been identified among World Trade Center responders. We wanted to study if this excess was associated with exposure to WTC dust
The results suggest that respiratory exposure to WTC dust can induce inflammatory and immune responses in prostate tissue. Chronic inflammation could facilitate prostate cancer development

Taken together, our results suggest that World Trade Center prostate cancer cases have a distinct gene expression pattern that may be the result of exposure to specific carcinogens during the WTC attacks. WTC dust-exposed rat prostate displayed unique changes in gene expression and immune cell infiltrates after acute dust exposure, suggesting that the effect of exposure may be measured locally in target organs such as prostate. In addition, some of the genes overexpressed in rat normal prostates as a consequence of exposure are also overexpressed in human prostate cancer tissues, suggesting a link between exposure, local immune dysregulation, and prostate cancer development Continue reading

Metagenomic Sequencing Enhanced Diagnosis of Meningitis and Encephalitis Infections

MedicalResearch.com Interview with:

Dr. Charles Chiu, M.D./Ph.D. Professor, Laboratory Medicine and Medicine / Infectious Diseases Director, UCSF-Abbott Viral Diagnostics and Discovery Center Associate Director, UCSF Clinical Microbiology Laboratory UCSF School of Medicine

Dr. Chiu

Dr. Charles Chiu, M.D./Ph.D.
Professor, Laboratory Medicine and Medicine / Infectious Diseases
Director, UCSF-Abbott Viral Diagnostics and Discovery Center
Associate Director, UCSF Clinical Microbiology Laboratory
UCSF School of Medicine

MedicalResearch.com: What is the background for this study? Would you describe what is meant by metagenomic sequencing?

Response: Metagenomic next-generation sequencing (mNGS) is the use of technology to generate millions of sequence reads to diagnose infection sin patients by characterizing the full range of potential pathogens (bacteria, viruses, fungi, and parasites) in a single sample. Although shown to be a promising diagnostic tool for  infectious diseases in case reports and limited case series (Chiu and Miller Nature Reviews Genetics 20, 341-355 (2019)), to date the “real-life” utility of this approach for patient care has hitherto not been demonstrated.  This study is the first prospective, multi-center study of clinical mNGS testing for the diagnosis of neurological infections in acutely ill hospitalized patients presenting with meningitis and/or encephalitis.

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Does Genetic Information Encourage Doctors to Switch Anticoagulation Medications?

MedicalResearch.com Interview with:

Thomas J. Povsic, MD, PhDInterventional CardiologistDuke Clinical Research InstituteDuke University School of MedicineDurham, North Carolina 

Dr. Povsic

Thomas J. Povsic, MD, PhD
Interventional Cardiologist
Duke Clinical Research Institute
Duke University School of Medicine
Durham, North Carolina 

MedicalResearch.com: What is the background for this study? 

Response: The background for this study is that it is unknown how mandatory reporting of CYP2C19 metabolizer status affects how doctors treat patients or to what degree provision of this information would affect choice of a P2Y12 inhibitor within a clinical trial.

As part of the GEMINI-ACS trial, all patients underwent CYP2C19 metabolizer testing.  This trial enrolled patients with a recent acute coronary syndrome and randomized them to aspirin or a low dose of rivaroxaban.  All patients were also to be treated with ticagrelor or clopidogrel, which was at the discretion of the investigator.  Investigators were given information regarding the CYP2C19 metabolizer status about a week after randomization.  Importantly prior to randomization, all investigators were asked how they expected to use this information, and then we followed what they actually did.

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Why Do Some People Get a Dog?

MedicalResearch.com Interview with:
Tove Fall PhD
Senior author of the study
Associate Professor in Epidemiology
Department of Medical Sciences and the Science for Life Laboratory
Uppsala University 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Dog ownership is common in the Western society but little is known about what actually makes people get a dog.

We conducted a twin study to understand whether the genetic make-up has an influence on this choice. We found that more than 50% of the differences in dog ownership is explained by genetic variants.  Continue reading

Genes Determine Why We Don’t All Smell the Same

MedicalResearch.com Interview with:

Dr. Casey Trimmer, PhDGeneticist, was a post-doctoral fellow at the Monell Center when the research was conducted

Dr. Trimmer

Dr. Casey Trimmer, PhD
Geneticist, was a post-doctoral fellow at the
Monell Center when the research was conducted

MedicalResearch.com: What is the background for this study?  

Response: We detect odors using 400 different types of sensor proteins, called olfactory receptors, in our noses. An odor molecule activates a specific combination of these receptors, and this pattern of activation gives us information on what we’re smelling–whether its floral or smoky, intense or weak, and how much we like it. However, how the system translates receptor activation to these perceptual features is largely unknown. Here, we take advantage of the extensive genetic variation in the OR gene family to understand the contribution of individual ORs to odor perception. By studying cases where the function of a particular OR is lost, we can examine what kinds of perceptual alterations occur, allowing us to link receptor to odor and understand what kind of information the receptor is encoding.

Data linking genetic variation to perceptual changes exist for only 5 ORs. Here, we examined the perceived intensity and pleasantness of 68 odors in 332 participants. We used next-generation genome sequencing to identify variants in 418 OR genes and conducted a genetic association analysis to relate this variation to differences in odor perception. We then use a cell-based assay to examine receptor function and investigate the mechanisms underlying our associations. Finally, we examined the contribution of single OR genotype, genetic ancestry, age, and gender to variations in odor perception.

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Machine Learning Can Analyze Entire Transcriptome To Improve Diagnosis of Difficult Cancers

MedicalResearch.com Interview with:

Steven J.M. Jones, Professor, FRSC, FCAHSCo-Director & Head, BioinformaticsGenome Sciences CentreBritish Columbia Cancer Research CentreVancouver, British Columbia, Canada

Dr. Jones

Steven J.M. Jones, Professor, FRSC, FCAHS
Co-Director & Head, Bioinformatics
Genome Sciences Centre
British Columbia Cancer Research Centre
Vancouver, British Columbia, Canada and

Jasleen Grewal, BSc.Genome Sciences CentreBritish Columbia Cancer Research CentreVancouver, British Columbia, CanadaJasleen Grewal, BSc.
Genome Sciences Centre
British Columbia Cancer Research Centre
Vancouver, British Columbia, Canada

MedicalResearch.com: What is the background for this study?

Response: Cancer diagnosis requires manual analysis of tissue appearance, histology, and protein expression. However, there are certain types of cancers, known as cancers of unknown primary, that are difficult to diagnose based purely on their appearance and a small set of proteins. In our precision medicine oncogenomics program, we needed an accurate approach to confirm diagnosis of biopsied samples and determine candidate tumour types for where the primary site of the cancer was uncertain.  We developed a machine learning approach, trained on the gene expression data of over 10,688 individual tumours and healthy tissues, that has been able to achieve this task with high accuracy.

Genome sequencing offers a high-resolution view of the biological landscape of cancers. RNA-Seq in particular quantifies how much each gene is expressed in a given sample. In this study, we used the entire transcriptome, spanning 17,688 genes in the human genome, to train a machine learning method for cancer diagnosis. The resultant method, SCOPE, takes in the entire transcriptome and outputs an interpretable confidence score from across a set of 40 different cancer types and 26 healthy tissues.  Continue reading

Nature vs Nurture? Environment Play a Bigger Role in Dental Cavities

MedicalResearch.com Interview with:

Katrina Scurrah MDMelbourne School of Population and Global Health

Dr. Scurrah

Katrina Scurrah PhD
Senior Research Fellow (Biostatistician), Twins Research Australia, and Melbourne School of Population and Global Health, The University of Melbourne and
Honorary Fellow, Murdoch Childrens Research Institute.

MedicalResearch.com: What is the background for this study?

Response: Oral health is an important component of general health and yet dental caries (decay) is still common in children (affecting up to one in three 5-6 year old children in Australia). Although we know that some genetic and lifestyle factors (such as diet) are important risk factors for caries, the relative importance of these is still unclear.  Risk factors from pregnancy and very early childhood (even before teeth appear) might also be important. This study is the first to include prospectively measured data on health and well-being from pregnancy, birth and early childhood in a study of twin children. We analysed data from a cohort of 172 pairs of twin children to assess the effects of genes and environment on susceptibility to dental caries at six years-of-age.

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Genetic Studies Can Help Determine How Low LDL Should Go With Treatment

Florian Kronenberg

Dr. Kronenberg

MedicalResearch.com Interview with:
Florian Kronenberg, MD
Division of Genetic Epidemiology
Department of Medical Genetics, Molecular and Clinical Pharmacology
Medical University of Innsbruck, Innsbruck, Austria

MedicalResearch.com: What is the background for this study?

Response: Lp(a) is one of the most prevalent lipoprotein risk factors for cardiovascular disease. Roughly 20% of the general Caucasian population have concentrations above 50 mg/dL and the 10% with the highest concentrations have a 2 to 3-fold increased risk for myocardial infarction.

There is strong evidence from genetic studies that high Lp(a) concentrations are causally related to cardiovascular outcomes. Until recently there was no drug available which lowers Lp(a) without any effects on other lipoproteins. This has recently changed by the development of drugs that block the production of Lp(a) in an impressive way. These drugs have to be studied in randomized controlled trials whether they not only lower Lp(a) concentrations but also cardiovascular outcomes. For the planning of such studies it is crucial to estimate the amount of Lp(a) lowering required to show a clinical benefit.

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Gene Linked to Colon Cancer in Younger Patients Identified

MedicalResearch.com Interview with:

Valentine N. Nfonsam, MD, MS, FACSAssociate Professor of SurgeryProgram Director, General Surgery ResidencyColon and Rectal SurgeryDivision of Surgical OncologyUniversity of Arizona, Tucson

Dr. Nfonsam

Valentine N. Nfonsam, MD, MS, FACS
Associate Professor of Surgery
Program Director, General Surgery Residency
Colon and Rectal Surgery
Division of Surgical Oncology
University of Arizona, Tucson 

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The overall incidence of colon cancer in the United states has gone down in the last few decades. However, there has been a significant increase in the incidence of sporadic colon cancer is young patients (<50 years old). The etiology of this phenomenon is likely multi-factorial.

These young patients do present with more advanced disease and with aggressive features. We demonstrated in our study that the colon cancer tumor biology was different between young and older patients. We also singled out a particular gene, Cartilage oligomeric Matrix Protein (COMP) which was significantly over-expressed in young patients and demonstrated its role in cancer proliferation and metastasis and also its potential as a prognostic biomarker since we were able to detect it in plasma.

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DNA Copy Number Variants Linked to Increased Risk of Depression

MedicalResearch.com Interview with:

Dr Kimberley Kendall MBBChWellcome Trust Clinical Research Fellow

Dr. Kendall

Dr Kimberley Kendall MBBCh
Wellcome Trust Clinical Research Fellow

Professor James WaltersMRC Centre for Neuropsychiatric Genetics and GenomicsProfessor, Division of Psychological Medicine and Clinical Neurosciences

Prof. Walters

Professor James Walters
MRC Centre for Neuropsychiatric Genetics and Genomics
Professor, Division of Psychological Medicine and Clinical Neurosciences

Cardiff University
 

MedicalResearch.com: What is the background for this study?

Response: Copy number variants (CNVs) are the deletion or duplication of large sections of DNA. Large, rare CNVs have been shown to increase the risk of neurodevelopmental disorders including autism spectrum disorder (ASD), intellectual disability (ID), attention deficit/hyperactivity disorder (ADHD) and schizophrenia. However, the impact of these CNVs on risk of depression was unclear from the existing literature. Continue reading

RNA Genetic Testing Improves Analysis of Hereditary Cancer Genes

MedicalResearch.com Interview with:
Rachid Karam, PhD

Director, Ambry Translational Genomics Lab
Ambry Genetics 

MedicalResearch.com: What is the background for this study?

Response: DNA genetic testing (DGT) for hereditary cancer genes is now a well accepted clinical practice; however, the interpretation of DNA variation remains a challenge to laboratories and medical providers.

RNA genetic testing (RGT) as a supplement to DGT is a means to clarify the clinical actionability of variants in hereditary cancer genes, improving our ability to accurately apply known strategies for cancer risk reduction.

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Bacteria in Intestinal Microbiome Freely Transfer Genes To Each Other

MedicalResearch.com Interview with:
Kyung Mo Kim

Senior research scientist
Korea Polar Research Institute.
Professor Gustavo Caetano-Anollés
Carl R. Woese Institute for Genomic Biology
University of Illinois
Arshan Nasir
Distinguished Fellow
Los Alamos National Laboratory in New Mexico

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Horizontal gene transfer is the process by which unrelated microorganisms can exchange genes. The famous examples would be transfer of antibiotic resistance genes among bacteria that renders many commercially expensive antibiotics useless. From an evolutionary point of view, it complicates our understanding of how bacteria are related since even distantly-related bacteria can share genes and then cluster together on evolutionary trees. Thus better understanding horizontal evolution is important for both public health and our basic understanding of microbial taxonomy and evolution.

There are some excellent existing methods of HGT detection that compare DNA features (e.g. GC%, codon usage) or statistical similarity between genomes to identify foreign genes. However, these methods work better to identify recently transferred genes. Transfers that happened millions or billions of years ago cannot be reliably detected since DNA sequences evolve over time during which foreign DNA can become more host-like. That is why we focused our attention on utilizing approaches that are based on sound evolutionary principles.

If a gene is horizontally acquired, then a phylogenetic tree of that gene will be different from the reference or known tree of the organisms. The true phylogenetic tree of organisms describes how organisms have descended from a common ancestor through inheritance of genes. If a gene is acquired from a source outside the parents or from an unrelated organism, then there will be a conflict between gene tree and the reference/known species tree. This conflict can be indication of HGT. Continue reading

Epilepsy: Genetic Testing Should Include Parental Sampling

MedicalResearch.com Interview with:

Dr. Ahmad Abou Tayoun, PhDClinical Molecular GeneticistDirector of the Genetics LaboratoryAl Jalila Children’sUnited Arab Emirates

Dr. Abou Tayoun

Dr. Ahmad Abou Tayoun, PhD
Clinical Molecular Geneticist
Director of the Genetics Laboratory
Al Jalila Children’s
United Arab Emirates

MedicalResearch.com: What is the background for this study?  

Response: In this study, we provide data in favor of using an exome-based testing approach, where parental samples can be readily accessible, for early onset epilepsy patients. The exome test includes all coding genes in the human genome. Although we perform exome sequencing on those patients, we demonstrate that a first tier analysis should include targeted interpretation of ~100 genes strongly associated with the disease. This analysis provides diagnoses in ~11% of the patients. Follow up parental testing on a limited number of patients (n=15) that had inconclusive results, revealed de novo (new mutations) variant status, leading to upgrade to positive reports in 7 patients and adding ~5% to the overall diagnostic yield.

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Genes Linked to Alcohol Use Disorder Identified

MedicalResearch.com Interview with:

Henry R. Kranzler, MDProfessor of PsychiatryPerelman School of MedicineUniversity of Pennsylvania

Dr. Kranzler

Henry R. Kranzler, MD
Professor of Psychiatry
Perelman School of Medicine
University of Pennsylvania

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Alcohol consumption and alcohol use disorder (AUD) are moderately heritable traits.  To date, genome-wide association studies (GWAS) have not examined these traits in the same sample, which limits an assessment of the extent to which genetic variation is unique to one or the other or shared.

This GWAS examined a large sample (nearly 275,000 individuals) from the U.S. Veterans Affairs Million Veteran Program (MVP) for whom data on both alcohol consumption and alcohol use disorder diagnoses were available from an electronic health record.  We identified 18 genetic variants that were significantly associated with either alcohol consumption, AUD, or both. Five of the variants were associated with both traits, eight with consumption only, and five with alcohol use disorder only.  Continue reading

Insulin Resistance Characterizes a Subset of Schizophrenia Patients

MedicalResearch.com Interview with:

Prof Sabine Bahn MD PhD MRCPsych FRSBCambridge Centre for Neuropsychiatric Research

Prof. Bahn


Prof Sabine Bahn MD PhD MRCPsych FRSB

Cambridge Centre for Neuropsychiatric Research

Jakub Tomasik, PhDDepartment of Chemical Engineering and Biotechnology

Dr. Tomasik

Jakub Tomasik, PhD
Department of Chemical Engineering and Biotechnology
University of Cambridge

 

MedicalResearch.com: What is the background for this study? What are the main findings? 

Response: Schizophrenia patients are at increased risk of impaired glucose metabolism, yet the comorbidity between the two conditions cannot be fully explained by known risk factors such as obesity, smoking, stress or antipsychotic medication. Previous family and genome-wide studies have suggested that the co-occurrence between schizophrenia and impaired glucose metabolism might be due to shared genetic factors, as exemplified by increased risk of diabetes in first-degree relatives of schizophrenia patients, but the biological mechanisms underlying this association remain unknown.

We examined the association between insulin resistance, schizophrenia polygenic risk and response to treatment in 58 drug-naive schizophrenia patients and 58 matched healthy individuals while controlling for a range of demographic (age, gender, body mass index), lifestyle (smoking, alcohol and cannabis use) and clinical (psychopathology scores, treatment drug) factors.

We found that insulin resistance, a key feature contributing to the development of type 2 diabetes, significantly correlated with schizophrenia polygenic risk score in patients, with higher genetic risk of schizophrenia associated with increased insulin resistance. Furthermore, we found that patients with higher insulin resistance were more likely to switch medication during the first year of treatment, which implies lower clinical response.  Continue reading

Pathogenic RET Variants Occur at Higher Prevalence Than Previously Recognized

MedicalResearch.com Interview with:

Emily J. Gallagher, MDAssistant Professor of MedicineEndocrinology, Diabetes and Bone DiseaseIcahn School of Medicine at Mount Sinai 

Dr. Gallagher

Emily J. Gallagher, MD
Assistant Professor of Medicine
Endocrinology, Diabetes and Bone Disease
Icahn School of Medicine at Mount Sinai 

MedicalResearch.com: What is the background for this study?

Response: Multiple Endocrine Neoplasia Syndrome Type 2 (MEN2) is an inherited endocrine disorder characterized by the development of pheochromocytoma, medullary thyroid carcinoma (MTC) and parathyroid tumors. It occurs due to activating missense variants in the RET gene.

The estimated prevalence of MEN2 is 1 per 30,000 in the general population. Through a collaboration between The Center for Genomic Health, the Charles Bronfman Institute for Personalized Medicine, and the Division of Endocrinology at Mount Sinai, our aim was to investigate the prevalence and clinical manifestations of pathogenic RET variants in the multi-ethnic BioMe Biobank.

The BioMe Biobank is an electronic health record-linked biobank with exome sequencing data available for more than 30,000 patients recruited across The Mount Sinai Health System.

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Genetic Mutation May Predict Outcomes of Prostate Cancer Treated With Androgen-Deprivation Therapy or Abiraterone

MedicalResearch.com Interview with:

Masaki Shiota MD, PhD Department of Urology, Graduate School of Medical Sciences Kyushu University Fukuoka , Japan

Dr. Shiota

Masaki Shiota MD, PhD
Department of Urology
Graduate School of Medical Sciences
Kyushu University
Fukuoka , Japan

MedicalResearch.com: What is the background for this study? What are the main findings?

Response:  3β-hydroxysteroid dehydrogenase-1 encoded by HSD3B1 is a rate-limiting enzyme required for all pathways of dihydrotestosterone synthesis, as well as converts abiraterone into Δ4-abiraterone (D4A), which blocks multiple steroidogenic enzymes and antagonizes the androgen receptor.

A mutation (1245A>C) in HSD3B1 is shown to be resistant to proteasomal degradation, causing substantial accumulation of this enzyme and gain-of-function. Although the HSD3B1 (1245C) allele can be acquired by mutation, germ-line single nucleotide polymorphism (SNP; rs1047303) is also known to exist. Then, in this study, we investigated the significance of missense polymorphism in HSD3B1 gene among men treated with primary ADT or abiraterone.

The results showed men carrying variant allele showed higher risk of progression in primary androgen-deprivation therapy, but vulnerable to abiraterone treatment. Continue reading

Genetics Could Explain Smokers’ Preference for Menthol Cigarettes

MedicalResearch.com Interview with:

Dennis Drayna, PhD Chief of the Laboratory of Communication Disorders and the Section on Genetics of Communication Disorders National Institute on Deafness and Other Communication Disorders Part of the National Institutes of Health

DR. Drayna

Dennis Drayna, PhD
Chief of the Laboratory of Communication Disorders and the Section on Genetics of Communication Disorders
National Institute on Deafness and Other Communication Disorders
Part of the National Institutes of Health

MedicalResearch.com: What is the background for this study?

Response: In the United States, there are striking racial differences in the rate of menthol cigarette use.  Tobacco use is a major preventable source of morbidity and mortality in the population, and menthol cigarette use by African Americans represents an important issue for attempts to address minority health disparities.

There have been many studies that have documented the role of inherited factors that contribute to smoking or tobacco use.  However, no studies have examined the role of genetic factors specifically in menthol tobacco use.  The preference for menthol cigarettes among African Americans has previously been attributed to cultural factors or industry advertising practices directed at this group.

In our study, we asked whether genetic factors could explain why African-American smokers choose menthol cigarettes over non-menthol cigarettes. Our initial hypothesis was that variation in genes that encode the known menthol receptors was important in this difference, although we designed our study to look at all 21,000 protein-coding genes in the genome.

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Mutations Linked to Scarring Hair Loss in African American Women Identified

MedicalResearch.com Interview with:

Cicatricial Alopecia Courtesy of Dr. Amy McMichael MD The Department of Dermatology Wake Forest Baptist Medical Center Winston-Salem, North Carolina 

Cicatricial Alopecia
Courtesy of Dr. Amy McMichael MD
The Department of Dermatology
Wake Forest Baptist Medical Center
Winston-SalemNorth Carolina

Eli Sprecher MD PhD
Professor and Chair, Division of Dermatology
Deputy Director General for R&D and Innovation
Tel Aviv Sourasky Medical Center
Frederick Reiss Chair of Dermatology
Sackler Faculty of Medicine
Tel Aviv University, Tel Aviv, Israel and

MedicalResearch.com: What is the background for this study?

Response: Central centrifugal cicatricial alopecia (CCCA) is a form of hair loss (alopecia) which is extremely common and affects one in every 20 women of African origin. It starts usually during the fourth decade of life. Because it can be inherited from mothers to their children, it is thought to have a genetic basis. On the other hand, it is known to mainly affect women who use to groom their hair intensively. Thus it was thought that the disease stems from some form of inherited susceptibility to the damage incurred to the hair follicle by grooming habits.

In the study we published, we searched for the genetic basis of CCCA.

In contrast with the common form of alopecia (androgenetic alopecia or female pattern alopecia), CCCA is associated with scarring of the scalp skin, which means that once hair is lost, it will likely not re-grow.

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Genes Help Determine Whether You Are Shaped Like an Apple or Pear

MedicalResearch.com Interview with:

Ruth Loos, PhD The Charles Bronfman Professor in Personalized Medicine Director, Genetics of Obesity and Related Traits Program Co-Director, Charles Bronfman Institute for Personalized Medicine Icahn School of Medicine at Mount Sinai New York, NY

Dr. Loos


Ruth Loos, PhD
The Charles Bronfman Professor in Personalized Medicine
Director, Genetics of Obesity and Related Traits Program
Co-Director, Charles Bronfman Institute for Personalized Medicine
Icahn School of Medicine at Mount Sinai
New York, NY

 

 

MedicalResearch.com: What is the background for this study? Which type of body fat distribution carries greater risk of diabetes or other obesity-related health disorders?

Response: Obesity broadly consists of two component; [1] there is overall body size (assessed using BMI) and [2] there is fat distribution (assessed using WHR). Both are “heritable”, which mean that they are in part determined by our genome (and the other part is determined by our lifestyle).

Over the past 15 years, geneticists have used an approach to screen the whole genome of thousands of people to identify genetic variations that differ between e.g. obese people vs non-obese people.

We have applied this approach to both components of obesity and have found so far that genes for “overall body size” seem to act in the brain, likely controlling hunger, satiety, reward, etc., whereas the genes that determine where in the body the excess fat will be stored when you gain weight (i.e. fat distribution) seem to act more “locally” at the fat cell level itself, determining the storage and release of fat.  Continue reading

12 Genetic Loci Associated with Human Healthspan

MedicalResearch.com Interview with:

Yurii Aulchenko Co-founder and Chief Scientist of PolyOmica

Yurii Aulchenko

Yurii Aulchenko Co-founder and Chief Scientist of PolyOmica
PolyOmica is a research & development company providing services and tools for quantitative genetics and functional genomics.

Peter Fedichev Founder and Chief Science Officer of Gero

Peter Fedichev

Peter Fedichev Founder and Chief Science Officer of Gero
Gero is a data-driven longevity company developing innovative therapies that will strongly extend the healthy period of life also known as healthspan

MedicalResearch.com: What is the background for this study? What are the main findings?

Peter Fedichev, Gero: Age is the most important risk factor behind age-related diseases and death. Lifespan has increased quite dramatically over the last 150-200 years mostly due to the eradication of early-life mortality. What we find, however, is that the healthspan, understood as the chronic diseases-free period, is also on the rise, but not so much. It appears that lifespan is modifiable by interventions, at least in lab animals. It is therefore crucial to understand if the biology behind human healthspan. Is it the same as that of lifespan? What are the molecular pathways and genetic factors controlling the healthspan? At the end, we would like to develop interventions that extend not only lifespan, but also the healthspan. Everyone wants to stay healthy!

Yurii Aulchenko, PolyOmica: We studied the incidence of the most prevalent age-related diseases in the large UK Biobank, one of the best repositories of biologically and medically relevant data from a very large cohort of aging individuals. We observed that the incidence (the chances of) all the major diseases increased exponentially with age. The diseases risk doubling time was about eight years, same as the mortality doubling time from the Gompertz mortality law, discovered as early as in 1825 and used in life insurance ever since. The similar patterns of age-dependent risk acceleration suggest a major common driver behind the diseases, that is most plausibly aging itself.

Peter Fedichev, Gero: The incidence of the diseases could, therefore, be used as a biomarker of aging process. We used the age at the onset of the first age-related disease (the end of healthspan) as the target for a genome-wide association study (GWAS) and identified as many as 12 genetic loci associated with human healthspan. Continue reading

Link Between Apolipoprotein E and Brain Hemorrhage Varies by Ethnicity

MedicalResearch.com Interview with:

Dr. Marini

Dr. Marini

Sandro Marini, MD
Research Fellow
Jonathan Rosand Laboratory
Massachusetts General Hospital
Boston, MA 02114

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: The epsilon(ε) 4 allele of the Apolipoprotein E (APOE) gene increases risk for Alzheimer’s disease (AD) and intracerebral hemorrhage (ICH).

In both diseases, it is believed to increase risk through the deposition of beta-amyloid within the brain and blood vessels, respectively. The effect of APOE ε4 on both AD and ICH risk changes across populations, for unclear reasons.

In our study, we confirmed the role of APOE ε4 for ICH risk in whites and found that the risk-increasing effect of the 4 allele is demonstrable in Hispanics only when balancing out the effect of hypertension.
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Polygenic Risk Scores Linked to Intelligence, ADHD and Brain Findings

MedicalResearch.com Interview with:

Silvia Alemany ,PhD first author Barcelona Institute for Global Health (ISGlobal), a centre supported by "la Caixa". In collaboration with co-authors:

Dr. Alemany

Silvia Alemany, PhD first author
Barcelona Institute for Global Health (ISGlobal), a centre supported by “la Caixa”.

In collaboration with co-authors:
Philip Jansen,MD, MSc and
Tonya White, MD, PhD
Erasmus University Medical Center, Rotterdam

MedicalResearch.com: What is the background for this study?

Response: Individuals affected by psychiatric disorders can demonstrate morphological brain abnormalities when compared to healthy controls. Although both genetic and environmental factors can account for these brain abnormalities, we expect that genetic susceptibility for psychiatric disorders has the greatest influence on the development of the brain.

Genetic susceptibility for psychiatric disorders can be estimated at the individual level by generating polygenic risk scores. Using this methodology, genetic susceptibility to psychiatric disorders and cognition has been associated with behavior problems in childhood. These findings suggest that heritable neurobiological mechanisms are at play in very early in the course of the illnesses.

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Tinnitus: Study of Adoptees Suggests Genetic Predisposition

MedicalResearch.com Interview with:

Christopher R. Cederroth | Ph.D. Docent Associate Professor Experimental Audiology | Department of Physiology and Pharmacology Karolinska Institutet  Sweden

Dr. Cederroth

Christopher R. Cederroth | Ph.D. Docent
Associate Professor
Experimental Audiology | Department of Physiology and Pharmacology
Karolinska Institutet
Sweden

MedicalResearch.com: What is the background for this study?

Response: Tinnitus is experienced is experienced by a large proportion of the population and affects more than 15% of the population worldwide (estimated 70 million people in Europe). However, for near 3% of the population, tinnitus becomes a chronic bothersome and incapacitating symptom. Severe tinnitus interferes with sleep, mood, and concentration and thus impacts life quality, ultimately leading to sick leave and disability pension. A high cost to society has been reported, and since the prevalence of tinnitus has been predicted to double in Europe by 2050, there is an important need for an effective treatment. And today there are none, with the exception of cognitive behavioral therapy, which helps coping with it but does not remove the tinnitus. There has been a number of innovative treatment approaches, but they are overall not successful and it is now agreed that it is likely because tinnitus is a heterogeneous condition – meaning that we cannot consider tinnitus a single entity but an ensemble of different forms or subtypes, which need to be defined.

Tinnitus has always been considered a condition influenced by environmental factors, but our initial studies suggested the opposite. Adoption studies are excellent in showing the influence of shared-environment effects and establish a genetic basis for a disease or a trait. It allows to test the transmission of a trait between the adoptee and their biological or their adoptive parent. Transmission via the biological parent is expected to be due to a heritable genetic effect, while transmission via the adoptive parent is associated with home-environment, the so-called shared-environmental effect. We used medical registry data to identify tinnitus patients and adoptees.

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Paternal Grandfather’s Access to Food Predicts All-Cause and Cancer Mortality in Grandsons

MedicalResearch.com Interview with:

Denny Vågerö  PhD MSc CHESS, Centre for Health Equity Studies Department of Public Health Sciences Stockholm University, Stockholm, Sweden

Dr. Vågerö

Denny Vågerö  PhD MSc
CHESS, Centre for Health Equity Studies
Department of Public Health Sciences
Stockholm University, Stockholm, Sweden

MedicalResearch.com: What is the background for this study? What are the main findings?

Response: Transgenerational, epigenetic, response, has been shown in studies of animals and plants. Does it apply to humans?

Previous findings of associations between grandparents early nutrition and grandchildren’s mortality have been controversial.  Two reasons for this: evidence in human studies has been based on rather small numbers and potential mechanisms are not very well understood.

We have tested the hypothesis that there is “a male line transgenerational response” to nutritional events in pre-puberty in a study much larger than previous ones.

We find support for this hypothesis in that boys who enjoyed unusually good access to food during their “slow growth period” (aged 9-12 years) seem to transmit a mortality risk on their grandsons but not granddaughters, in particular for cancer.

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Some Anti-Tumor Drugs May Promote Delayed Aggressive Cancers

MedicalResearch.comInterview with:
Alexandra Avgustinova PhD
Postdoctoral fellow at the Institute for Research in Biomedicine (IRBBarcelona)

Dr. Avgustinova
Dr. Avgustinova

MedicalResearch.com:  What is the background for this study?

Response: The basis of this study was the strong association between closed chromatin and high mutation rate reported several years ago. We were surprised to see this observation being widely interpreted as a causal association, as it was largely based on correlative studies without experimental backing. Therefore we decided to experimentally test for the first time whether indeed altering chromatin opening would affect mutation rate or distribution within tumours.

MedicalResearch.com: What are the main findings?

Response: We found that, despite significantly increasing chromatin opening, loss of the histone methyltransferase G9a did not have any major influence on the mutation rate or distribution within cutaneous squamous cell carcinomas. These results demonstrate that chromatin opening does not play a major role in determining the mutation rate within tumours, and we speculate that other, confounded factors (e.g. replication timing or H3K36me3 levels) are likely causal for the observed association. This, however, remains to be proven experimentally.

Another major conclusion of our study was that although tumour initiation was delayed and tumour burden decreased in the absence of G9a, the tumours that did develop were highly aggressive due to selection for more aggressive tumour clones. This finding was contrary to many published reports suggesting G9a as a good candidate for clinical targeting, highlighting the need for long-term follow-up in pre-clinical studies.

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Using of Big Data to Estimate Prevalence of Defective DNA Repair Variants in the US

MedicalResearch.com Interview with:

Kenneth H. Kraemer,M.D.
Chief DNA Repair Section
Laboratory of Cancer Biology and Genetics, Center for Cancer Research
National Cancer Institute

MedicalResearch.com:  What is the background for this study?

Response: At the National Cancer Institute, we have been examining patients with xeroderma pigmentosum (XP), a rare, recessively inherited, cancer-prone disease for many years. Therefore, with the increasing use of exome sequencing, we decided to see how closely”big data” corresponded with our clinical observations.  

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Genome Analysis Can Overestimate Incidence of Chronic Kidney Disease

MedicalResearch.com Interview with:

Hila Milo Rasoul, PhD Postdoctoral research scientist Ali Gharavi Lab Columbia University

Dr. Milo Rasouly

Hila Milo Rasouly, PhD
Postdoctoral research scientist
Ali Gharavi Lab
Columbia University

MedicalResearch.com: What is the background for this study?

Response: Genome sequencing is increasingly used in clinical medicine to help make a clinical diagnosis and make predictions about potential future complications. The diagnostic yield and limitations for different indications are still being worked out.  We are interested in studying the applications of genome sequencing for chronic kidney diseases. It is estimated that 10% of adults have chronic kidney disease (CKD), and amongst them, 10% are caused by single-gene (Mendelian) forms of disease.

The American College of Medical Genetics and Genomics developed guidelines on how to interpret genetic variants in order to make a genetic diagnosis. Our lab has been engaged in studying the yield and impact of genetic testing for  CKD, and in the course of our research, we realized that a very large number of individuals have genetic variants that may be classified as pathogenic based on automated application of the guidelines. However, in majority of these cases, the genetic variant was much too frequent in the population to be plausibly disease-causing or did not match up well with the clinical diagnosis. This led us to wonder about the risk of false-positive genetic diagnosis. To analyze this risk for false-positive genetic diagnosis, we analyzed the genome sequence of 7,974 self-reported healthy adults.

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Eczema Determined by Genetics or Environment?

MedicalResearch.com Interview with:
“Eczema” by NIAID is licensed under CC BY 2.0Hans Bisgaard, MD, DMSc

Professor of Pediatrics
C‌openhagen U‌niversity H‌ospital, H‌erlev-G‌entofte
Copenhagen

MedicalResearch.com: What is the background for this study? What are the main findings?

 Response: The uniqueness of this study, is that we for the first time have day-to-day recordings of symptoms and use og local treatment during the first 3 years of life showing the disease peaks at 2 years of age and children start outgrowing thereafter.Previous studies including our own have analyzed eczema at a certain age.Since eczema is highly variable over time, our disease description is novel.This has allowed us a more reliable analyses of factors determining eczema in young children 

MedicalResearch.com: What should readers take away from your report?

Response: What we see it that eczema is determined by genetics and with no know external factors causing or deteriorating the severity.

 MedicalResearch.com: What recommendations do you have for future research as a result of this work?

Response: We are currently aiming to analyze the interaction between genetics and the environment. In other words though eczema is highly genetically determined, we have reason to believe that external factors triggers such genes.
 No conflicts of interest   

Citation:  

Thorsteinsdottir S, Stokholm J, Thyssen JP, et al. Genetic, Clinical, and Environmental Factors Associated With Persistent Atopic Dermatitis in Childhood. JAMA Dermatol. Published online November 14, 2018. doi:10.1001/jamadermatol.2018.4061

 

Nov 15, 2018 @ 12:52 pm

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