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

  The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website. 

Panel of Salivary RNA Biomarkers Could Identify Autism

MedicalResearch.com Interview with:

Steven D. Hicks, M.D.,Ph.D Department of Pediatrics Penn State College of Medicine Hershey, PA

Dr. Hicks

Steven D. Hicks, M.D.,Ph.D
Department of Pediatrics
Penn State College of Medicine
Hershey, PA

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

Response: Since autism has both genetic and environmental underpinnings, my colleagues and I suspected that transcriptional elements (e.g. regulatory RNA molecules) might be different in the saliva of children with autism compared to peers without autism. We used a non-biased approach to analyze saliva from 372 children, and allowed machine learning techniques to inform which RNA elements best predicted autism status. To our surprise, microbial RNA levels and human RNA levels were equally powerful in predicting which children had autism. This may be because some children with autism eat restricted diets, resist tooth brushing, or put foreign objects in their mouths. The end result was a panel of 32 RNAs (20 human and 12 bacterial) that identified autism with 87% accuracy. Interestingly, when we tested the panel in a completely separate set of 84 children (including children from a different geographic region) the accuracy remained 88%. 

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Genetic Variant is Risk Factor for Two Different Types of Interstitial Lung Disease

MedicalResearch.com Interview with:

Joyce S. Lee, MD Associate Professor Director, Interstitial Lung Disease Program Department of Medicine Division of Pulmonary Sciences and Critical Care Medicine University of Colorado School of Medicine

Dr. Lee

Joyce S. Lee, MD
Associate Professor
Director, Interstitial Lung Disease Program
Department of Medicine
Division of Pulmonary Sciences and Critical Care Medicine
University of Colorado School of Medicine

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

Response: Rheumatoid arthritis (RA) is a common inflammatory arthritis that can be complicated by interstitial lung disease (ILD). Patients with RA-ILD share clinical characteristics with another ILD called idiopathic pulmonary fibrosis (IPF).

Given the similar clinical phenotype, our goal was to see if these lung diseases (IPF and RA-ILD) shared a common genetic risk factor. The MUC5B promoter variant is the most common risk factor (genetic and otherwise) for the development of IPF.

Our findings demonstrate the MUC5B promoter variant is also a strong risk factor for the development of RA-ILD among patients with RA.

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Is Pregnancy a “Stress Test” for Future Dementia Risk?

MedicalResearch.com Interview with:
"Pregnancy 1" by operalynn is licensed under CC BY 2.0Heather Boyd, Ph.D.
Senior researcher
Department of Epidemiology Research
Copenhagen Denmark

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

Response: We have known for a while that women who have had preeclampsia report different types of cognitive impairment (difficulties with short-term memory, attention deficits) in the years and decades after their pregnancies, and there are a few imaging studies suggesting that these women may have more white matter lesions in the brain and more signs of brain atrophy than women with uncomplicated pregnancies. We also know that women who have had preeclampsia are at increased risk of cardiovascular disease in the years and decades after delivery. Taken together, it was not a great leap to hypothesize that women with a history of preeclampsia might also be at increased risk of dementia later in life. However, the existing epidemiological data were unconvincing, possibly because it takes a great deal of power (a very large study population) to study links between two conditions that often occur decades apart.

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Genetic Locus Linked to Migraine Risk in African American Children

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
PhiladelphiaPennsylvania

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.  Continue reading

Strong Genetic Component to Psychotic-Like Experiences with Cannabis

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.  Continue reading

Paternal Smoking Can Affect Multiple Generations of Descendants

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.  Continue reading

Who Might Benefit From Early Screening for Colorectal Cancer?

MedicalResearch.com Interview with:

Mohammad Bilal, MD University of Texas Medical Branc

Dr. Bilal

Mohammad Bilal, MD
University of Texas Medical Branch

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

Response: Colorectal cancer (CRC) is the fourth most commonly diagnosed cancer among adults in the United States and the second leading cause of cancer related deaths. Recent studies have shown an increasing incidence of CRC in younger patients. This has led to increasing interests in identifying patient populations who might be at increased risk of developing CRC.

The U.S. Multi-Society Task Force of Colorectal Cancer (MSTF) recommends that CRC screening should begin at age 50 in average-risk persons. However, recently the American Cancer Society (ACS) have published recommendations to begin CRC screening at age 45 years in average risk patient population.

These recommendations were primarily based of modeling studies since there is little outcomes data in younger age groups in regards to prevention and detection of CRC. Despite these new recommendations from the ACS, there is limited direct evidence to support CRC screening at a younger age. In our study, we have evaluated the predictors of increased prevalence of adenomas in the 40 to 49-year-old individuals undergoing colonoscopy.  Continue reading

Breast Cancer: Gene Expression of Receptors on a Chip Can Enhance Precision Diagnosis

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. Continue reading

Why Are So Many People Near-Sighted?

MedicalResearch.com Interview with:
Andrei V. Tkatchenko, M.D., Ph.D.
Associate Professor
Columbia University Medical Center
Edward S. Harkness Eye Institute
New York, NY 10032

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

Response: Clear distance vision is rapidly becoming a rare privilege around the world, especially in Asia, due to increasing prevalence of myopia.

Although much effort has been directed towards elucidating the mechanisms underlying refractive eye development and myopia, treatment options for myopia are mostly limited to optical correction, which does not prevent progression of myopia or pathological blinding complications often associated with the disease. During early childhood development, the axial length of the eye normally grows to match its optical power in a process called emmetropization, producing focused images on the retina. However, very often environmental and genetic factors lead to a mismatch between the optical power of the eye and its axial length resulting in the development of myopia if eyes grow too long for their optical power. Experimental studies in many animal species suggest that emmetropization is regulated by optical defocus. The eye can compensate for imposed negative and positive optical defocus by increasing or decreasing its growth rate, respectively. However, the molecular mechanisms underlying emmetropization are poorly understood which prevents development of anti-myopia drugs.

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Genetic Risk Score Improves Ability To Predict Diabetics at Risk of Coronary Disease

MedicalResearch.com Interview with:

Mario Luca Morieri

Dr. Morieri

Mario Luca Morieri MD
Section on Genetics and Epidemiology, Research Division, Joslin Diabetes Center
Department of Medicine, Harvard Medical School, Boston, MA

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

Response: Coronary artery disease (CAD) is one of the most important complications of diabetes.

Similarly to other complex disorders, CAD is influenced by both environmental and genetic factors. Over the last decade, our understanding of the genetic factors contributing to CAD has dramatically improved and hundreds of new genetic markers associated with increased cardiovascular risk have been identified.

In this study, we showed that combining these genetic markers into a single score (a so called genetic risk score) can improve our ability to the identify those patients with type 2 diabetes who are at higher risk of experiencing a coronary event. 

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

Response: One take-away message is that the genetic markers associated with CAD in persons without diabetes have a similar effect in people with diabetes. Another is that prediction of increased risk of CAD in people with diabetes can be improved with the combination of genetic markers with “classic” known markers of CAD such as high cholesterol and high blood pressure. Improving cardiovascular risk prediction will allow physicians to focus their effort on people at higher risk, making the allocation of health-care resources more efficient. 

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

Response: We were able to replicate our findings (from the ACCORD trial) in another study including diabetic patients with similar characteristics (the ORIGIN trial). However, to improve the generalizability of the genetic risk score, its performance should be tested in populations with different clinical characteristics. With the detailed information provided in the paper, other researchers should be able to do this. Also, the genetic score reported in our paper applies to Whites as it was derived from genetic markers discovered in that ethnic group. It would be important to build a similar genetic risk score for people of different ancestry using genetic markers specific to those populations.

MedicalResearch.com: Is there anything else you would like to add? 

Response: We showed in the paper that the identification of an increasing number of genetic markers of CAD risk over the last 8 years has resulted into a progressive improvement in the performance of genetic risk scores for prediction of CAD risk. Thus, if new genetic markers of CAD continue to be identified over the next few years, the usefulness of these genetic scores may continue to increase. 

Citation:

Genetic Tools for Coronary Risk Assessment in Type 2 Diabetes: A Cohort Study From the ACCORD Clinical Trial

Mario Luca Morieri, He Gao, Marie Pigeyre, Hetal S. Shah, Jennifer Sjaarda, Christine Mendonca,Timothy Hastings, Patinut Buranasupkajorn, Alison A. Motsinger-Reif, Daniel M. Rotroff, Ronald J. Sigal,Santica M. Marcovina, Peter Kraft, John B. Buse, Michael J. Wagner, Hertzel C. Gerstein, Josyf C. Mychaleckyj, Guillaume Parè and Alessandro Doria

Diabetes Care 2018 Sep; dc180709.https://doi.org/10.2337/dc18-0709

Sep 29, 2018 @ 6:39 pm 

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Breastfeeding May Alter Gene That Influences How Children Deal With Stress

MedicalResearch.com Interview with:

Barry M. Lester, PhD Center for the Study of Children at Risk Warren Alpert Medical School, Brown University Women and Infants Hospital of Rhode Island Providence, Rhode Island;

Dr. Lester

Barry M. Lester, PhD
Center for the Study of Children at Risk
Warren Alpert Medical School, Brown University
Women and Infants Hospital of Rhode Island
Providence, Rhode Island;
 

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

Response: We know from rodent studies that maternal care or nurturing behavior can change the rat pups physiologic response to stress. More nurturing behavior makes it easier for rat pups to relax after stress. Not only that, these changes are permanent, they last into adulthood and there is evidence that these changes can be passed on to the next generation. With animal studies you can unlock the mechanism for this in ways that you can’t do with humans and we know from the rodent studies that the mechanism for these changes has to do with changes in gene activity.

Nurturing behavior controls a specific gene that regulates the infant’s physiological response to stress. In other words, we are looking at maternal behavioral programming of a gene that can make, in our case, a human infant less physiologically reactive to stress.

The physiological reactivity to stress that we studied was the production of the stress hormone cortisol. Cortisol is part of the body’s flight or fight reaction, the body’s major response to stress and too much or too little cortisol can be harmful and is related to a wide range of mental and physical health disorders in children and adults. The concerns about separating immigrant children from their parents that we read about every day in the paper are based on this same physiological system, where brain structures that control cortisol production are damaged by the stress of separation. 

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Most Patients Who Carry BRCA1/2 Pathogenic Variants Are Unaware

MedicalResearch.com Interview with:

Michael F. Murray, MD, FACMG, FACP Director for Clinical Operations in the Center for Genomic Health Yale School of Medicine

Dr. Murray

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.  Continue reading

Age, Sex and Genetics Can Identify Groups at Higher Risk of Alzheimer’s Disease

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

Dr. Frikke-Schmidt

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) Continue reading

Significant Sex Differences in Genetic Associations with Longevity

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 Sciences

Dr. Yi Zeng

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.

Continue reading

Breast and Ovarian Cancers: More Genes Than BRCA1 and BRCA2

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.   Continue reading

Women Whose Mothers Lived to 90, Likely To Have Health Old Age

MedicalResearch.com Interview with:

Aladdin H. Shadyab, PhD  MS, MPH, CPH Department of Family and Preventive Medicine UCSD twitter.com/TheDrAladdin

Dr. Aladdin Shadyab

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.

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Study Identifies Gene Mechanism Linked to Fear and Aggression

MedicalResearch.com Interview with:

Prof. Carmen Sandi Director, Brain Mind Institute Laboratory of Behavioral Genetics Brain Mind Institute Ecole Polytechnique Federale de Lausanne Lausanne, Switzerland 

Prof. Sandi

Prof. Carmen Sandi
Director, Brain Mind Institute
Laboratory of Behavioral Genetics
Brain Mind Institute
Ecole Polytechnique Federale de Lausanne
Lausanne, Switzerland 

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

Response: We are interested in understanding how the brain regulates social behaviors and aggression, both in healthy individuals and individuals with psychiatric disorders. In our recent publication in Molecular Psychiatry, we investigated the impact of an alteration in a gene, St8sia2, that plays important roles during early brain development. Alterations in this gene have been linked with schizophrenia, autism and bipolar disorder, and individuals with these disorders frequently present high aggressiveness. In addition, expression of this gene in the brain can be altered by stressful insults during very early life and development.

Our study shows that genetic and environmental conditions linked to a reduction in the expression of this neuroplasticity gene during early life can lead to impaired fear learning and associated pathological aggression. We could further reveal that deficits in St8sia2 expression lead to a dysfunction in a receptor in the amygdala (a brain region critically involved in emotionality and fear learning), the GluN2B subunit of NMDA Receptors.

This allowed us to target this receptor with D-cycloserine, a drug that facilitates NMDA receptor function. This treatment, when given acutely, ameliorated the capacity to learn from adversity and reduced individuals’ aggressiveness.  Continue reading

Genes From Dad Influence How Mom Cares for Babies

MedicalResearch.com Interview with:
“Family” by IsaacVakeroKonor is licensed under CC BY 3.0Professor Rosalind John
Head of Biomedicine Division, Professor
School of Biosciences
Cardiff University
Cardiff UK

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

Response: I have been studying a really remarkable family of genes called “imprinted genes” for the last 20 years. For most genes, we inherit two working copies — one from our mother and one from our father. But with imprinted genes, we inherit only one working copy – the other copy is switched off by epigenetic marks in one parent’s germline. This is really odd because we are all taught at school that two copies of a gene are important to protect us against mutations, and much safer than only one copy. So why turn off one copy?

Maternal care boosted by paternal imprinting in mammals

Maternal care boosted by paternal imprinting in mammals

When my research group were studying these genes in mice, we found out that one of them, called Phlda2, plays an important role in the placenta regulating the production of placental hormones. Placental hormones are critically important in pregnancy as they induce adaptations in the mother required for healthy fetal growth. There was also some indirect evidence that placental hormones play a role in inducing maternal instinct. Women are not born with a maternal instinct –  this behaviour develops during pregnancy to prepare the mother-to-be for the new and demanding role of caring for her baby. This led to my idea that this gene expressed in the offspring’s placenta could influence maternal behaviour, which was entirely novel. 

Until now direct experimental evidence to support the theory that placental hormones trigger this “motherly love” by acting directly on the brain of the mother has been lacking. To test the theory that our imprinted gene could influence the mother’s behaviour by regulating placental hormones, we generated pregnant mice by IVF carrying embryos with different copies of Phlda2. We used IVF to keep all the mothers genetically identical. This resulted in genetically identical pregnant female mice exposed to different amounts of placental hormones – either low, normal or high.

We found that female mice exposed in pregnancy to low amounts of placental hormones were much more focused on nest building (housekeeping) and spent less time looking after their pups or themselves than normal mice. In contrast, female mice exposed to high placental hormones neglected their nests and spent more time looking after their pups and more time self-grooming. We also found changes in the mother’s brain before the pups were born so we know that the change in priorities started before birth. 

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

Response: This study is important because it shows, for the first time, that genes from the dad expressed in the placenta influence the quality of care mothers gives to their offspring. Perhaps more significantly, this study highlights the importance of a fully functional placenta for high quality maternal care.

We have shown in a mouse model that genes in the placenta and placental hormones are important for priming maternal nurturing in an animal model. Human placenta have the same imprinted genes and also manufactures placental hormones. It is possible that problems with the placenta could misprogram maternal nurturing in a human pregnancy and these mothers may not bond well with their newborn. It is also possible that problems with the placenta could contribute to depression in mothers. We are all familiar with postnatal depression but many more mothers experience depression in pregnancy with 1 in 7 mothers reporting clinically significant symptoms. 

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

Response: After we found out that Phlda2 could influence maternal behaviour in mice, we asked whether there were changes in this gene in human placenta from pregnancies where women were either diagnosed with clinical depression or self reported depression in pregnancy. Phlda2 seems to be OK but we found another gene that belongs to the same imprinted gene family called PEG3 that is expressed at lower than normal levels in women with depression. Strangely, this seems to only be in placenta from boys. 

MedicalResearch.com: Is there anything else you would like to add?

Response: To explore this further, we have just started our own human cohort study called “Grown in Wales” at Cardiff University focused on prenatal depression. We are now looking at placental hormones in the mother’s blood and gene expression in the placenta to test the idea that the genes we are studying in mice are misregulated in the placenta of pregnancies where the mothers suffer with depression. This work is now funded by the Medical Research Council.

Citation: 

Maternal care boosted by paternal imprinting in mammals

D. J. Creeth, G. I. McNamara,, S. J. Tunster, R. Boque-Sastre,, B. Allen,, L. Sumption, J. B. Eddy,A. R. Isles, R. M. John PLOS
Published: July 31, 2018

Aug 2, 2018 @ 11:48 pm 

The information on MedicalResearch.com is provided for educational purposes only, and is in no way intended to diagnose, cure, or treat any medical or other condition. Always seek the advice of your physician or other qualified health and ask your doctor any questions you may have regarding a medical condition. In addition to all other limitations and disclaimers in this agreement, service provider and its third party providers disclaim any liability or loss in connection with the content provided on this website.

 

Alzheimer’s Disease: Genes Modify Effect of High Fat Diet

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. “

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PITS Gene Linked To Rare Neurologic Disorders

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

Dr. Marcogliese

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 Pediatric Medical Genetics Specialist Division of Medical Genetics, Department of Pediatrics Duke University School of Medicine, Durham, NC

Dr. Peña


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.

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Genetic Testing Could Identify Individuals At Risk of Osteoporosis

MedicalResearch.com Interview with:

Stuart Kim - PhD Professor of Developmental Biology, Emeritus Bio-X Affiliated Faculty James H. Clark Center Stanford University

Dr. Kim

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. Continue reading

Novel Models of Late-Onset Alzheimer’s Disease Based on GWAS

MedicalResearch.com Interview with:

Gregory Carter

Dr. Carter

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.  Continue reading

Whole-Exome Analysis of Late-Onset Alzheimer’s Disease Reveals Novel Candidate Genes Involved in Cognitive Function

MedicalResearch.com Interview with:

Dr. Carter

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.  Continue reading

Changing One Gene in One Gut Bacteria Altered Metabolism and Weight Gain (in mice)

MedicalResearch.com Interview with:

A. Sloan Devlin, PhD Assistant Professor Department of Biological Chemistry and Molecular Pharmacology Harvard Medical School

Dr. Devlin

A. Sloan Devlin, PhD
Assistant Professor
Department of Biological Chemistry and Molecular Pharmacology
Harvard Medical School

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

Response: It is known that the microbiome, the collection of bacteria that live in and on our bodies, influences the development of metabolic diseases including diabetes and obesity. The ways in which the microbiome affects host metabolism, however, are poorly understood. One reason for this lack of understanding is because the gastrointestinal tract contains hundreds of species of bacteria producing many different kinds of metabolites. Untangling the effects of these bacteria and the molecules they make is a significant challenge.

In this study, we decided to concentrate on a group of metabolites found in the human gut called bile acids. When we eat a meal, these compounds are released into the gastrointestinal tract where they act as detergents that aid in digestion. Once these molecules reach the lower gastrointestinal tract, the gut bacteria residing there chemically modify these compounds, producing a pool of over 50 different bile acids total.

Imbalances in this bile acid pool are thought to influence the progression of diet-induced obesity. However, it is unclear which specific bile acids are responsible for either beneficial or detrimental effects on host metabolism. We set out to address this question by first identifying a selective type of bacterial enzyme called a bile salt hydrolase, then by genetically deleting this enzyme from a common gut bacterium and investigating how this change affected host metabolism.

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