Author Interviews, Genetic Research, Weight Research / 02.06.2016
West-African Genetic Ancestry Associated with Protection Against Obesity in Men
MedicalResearch.com Interview with:
[caption id="attachment_24863" align="alignleft" width="95"]
Dr. Yann Klimentidis[/caption]
Dr. Yann C. Klimentidis PhD
Assistant Professor
Epidemiology and Biostatistics Department
The University of Arizona
Tucson, AZ 85724
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Klimentidis: There is a large gender disparity in obesity rates among African-Americans. African-American women have much higher rates of overweight and obesity as compared to African-American men. We hypothesized that genetic factors may partly explain this difference. So we tested whether the influence of West-African genetic ancestry on obesity differed among men and women. We found that greater West-African genetic ancestry was associated with protection against central obesity in men, but no such effect was observed in women.
Dr. Yann Klimentidis[/caption]
Dr. Yann C. Klimentidis PhD
Assistant Professor
Epidemiology and Biostatistics Department
The University of Arizona
Tucson, AZ 85724
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Klimentidis: There is a large gender disparity in obesity rates among African-Americans. African-American women have much higher rates of overweight and obesity as compared to African-American men. We hypothesized that genetic factors may partly explain this difference. So we tested whether the influence of West-African genetic ancestry on obesity differed among men and women. We found that greater West-African genetic ancestry was associated with protection against central obesity in men, but no such effect was observed in women.
Dr. Clara van Karnebeek[/caption]
Dr. Clara van Karnebeek PhD
Certified Pediatrician and Biochemical Geneticist at the BC Children’s Hospital
Principal Investigator, University of British Columbia
MedicalResearch.com: What is the background for this study?
Dr. van Karnebeek: The goal of the study was to diagnose patients with genetic conditions and discover and describe new diseases with potential for treatment. The study included patients with neurodevelopmental conditions that doctors suspected were genetic or metabolic in origin but had not been diagnosed using conventional methods. Our team tested the children and their parents using a combination of metabolomic (large scale chemical) analysis and a type of genomic sequencing called whole exome sequencing. With this state-of-the-art technique, experts analyze and interpret the portion of DNA called genes that hold the codes for proteins.
Some people’s intellectual disability is due to rare genetic conditions that interfere with the processes the body uses to break down food. Because of these metabolic dysfunctions, there is an energy deficit and build-up of toxic substances in the brain and body leading to symptoms such as developmental and cognitive delays, epilepsy, and organ dysfunction. Some of these rare diseases respond to treatments targeting the metabolic dysfunction at the cellular level and range from simple interventions like dietary modifications, vitamin supplements and medications to more invasive procedures like bone marrow transplants. Because the right treatment can improve cognitive functioning or slow or stop irreversible brain damage, early intervention can improve lifelong outcomes for affected children and their families.
Dr. Sibaji Sarkar[/caption]
Sibaji Sarkar Ph.D
Instructor of medicine
Boston University School of Medicine
Boston
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Sarkar: Although breast and ovarian cancers have different clinical presentations, there are certain molecular events that are conserved between the two types of cancers. For example, mutation in a few genes, such as BRCA1, BRCA2, is an indicator of possible development of both breast and ovarian cancers. ARHI, a pro-apoptotic imprinted gene is epigenetically silenced in both breast and ovarian cancers. A similar pattern was observed in microRNA as well. There are also several genes which are differentially expressed in these two types of cancers but few of these striking resemblances led us to investigate whether they have a common origin. In this paper, we compared genetic and epigenetic events in both breast and ovarian cancers and we hypothesize that they may have similar origin (mechanism of formation of cancer progenitor cells), which should be regulated by epigenetic mechanism.
Dr. Annette Schürmann[/caption]
Prof-Dr. Annette Schürmann
Department of Experimental Diabetology
German Institute of Human Nutrition Potsdam-Rehbruecke
Nuthetal, Germany
MedicalResearch.com: What is the background for this study?
Dr. Schürmann: The aim of our study was to clarify why genetically identical mice respond very different to a high fat diet. Some of the mice react with an elevated body weight, others not. We analyzed the expression pattern
of liver at two time points, at the age of 6 weeks, (the earliest time
point to distinguish between those that respond to the diet (responder
mice) and those that did not (non-responders)), and at the age of 20
weeks. One transcript that was significantly reduced in the liver of
responder mice at both time points was Igfbp2. The reason for the
reduced expression was an elevated DNA-methylation at a position that is
conserved in the mouse and human sequence. The elevated DNA-methylation
of this specific site in human was recently described to associate with
elevated fat storage (hepatosteatosis) and NASH. However, as 6 weeks old
mice did not show differences in liver fat content between responder and
non-responder mice we conclude that the alteration of Igfbp2 expression
and DNA methylation occurs before the development of fatty liver.
Our data furthermore showed that the epigenetic inhibition of Igfbp2
expression was associated with elevated blood glucose and insulin
resistance but not with fatty liver.
Dr. Geoffrey Liu[/caption]
Dr. Geoffrey Liu, MD MSC
Princess Margaret Hospital/Ontario Cancer Institute
University of Toronto
Toronto, Ontario
Canada
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Liu: Cetuximab is a monoclonal antibody therapy used in metastatic colorectal cancer patients when other chemotherapy options have been exhausted. Currently, the only useful biomarker to determine whether metastatic colorectal cancer patients will benefit from the drug, cetuximab, is whether patients carry a RAS mutation in their tumours. We evaluated additional biomarkers using samples from a Phase III clinical trial led by the Canadian Cancer Trials Group and the Australasian Gastrointestinal Trials Group. Our study identified a germline, heritable biomarker, a FCGR2A polymorphism, that further identifies an additional subgroup of patients who would benefit most from receiving cetuximab. This is important because the drug does have toxicity and is expensive to use; patients who are found not to likely benefit from this drug can go on quickly to try other agents, including participation in clinical trials.
Dr. Katarina Truvé[/caption]
Katarina Truvé PhD
Swedish University of Agricultural Sciences and
Kerstin Lindblad-Toh
Uppsala University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Truvé: Gliomas are malignant brain tumors that are rarely curable. These tumors occur with similar frequencies in both dogs and humans. Gliomas in dogs are strikingly similar at the biological and imaging level to human tumor counterparts. Some dog breeds such as Boxer and Bulldog are at considerably higher risk of developing glioma. Since these breeds at high risk are recently related, they are most likely carrying shared genetic risk factors. Our goal was therefore to use the dog genome to locate genes that may be involved in the development of glioma in both dogs and humans. We found a strongly associated locus and identified three candidate genes, DENR, P2RX7 and CAMKK2 in the genomic region. We have shown that CAMKK2 is lower expressed in glioma tumors than normal tissue in both dogs and human, and it has been reported that the associated canine mutation in P2RX7 results in a decrease in receptor function.
Dr-Daniel Benjamin[/caption]
Dr. Daniel J. Benjamin PhD
Associate Professor (Research), USC, 2015-present
Associate Professor (with tenure), Cornell, 2013-2015
Assistant Professor, Cornell University, 2007-2013
Research Associate, NBER, 2013-present
Faculty Research Fellow, NBER, 2009-2013
MedicalResearch.com: What is the background for this study?
Dr. Benjamin: Educational attainment is primarily determined by environmental factors, but decades of twin and family studies have found that genetic factors also play a role, accounting for at least 20% of variation in educational attainment across individuals. This finding implies that there are genetic variants associated statistically with more educational attainment (people who carry these variants will tend on average to complete more formal education) and genetic variants associated statistically with less educational attainment (people who carry these variants will tend on average to complete less formal education). But none of these genetic variants had been identified until our 2013 paper on educational attainment. That paper, which studied a sample of roughly 100,000 individuals, identified 3 genetic variants associated with educational attainment, each of which has a very small effect. In the current paper, we expanded our sample to roughly 300,000 individuals, with the goal of learning much more about the genetic factors correlated with educational attainment.
Dr. Han Liang[/caption]
Dr. Han Liang PhD
Associate Professor and Deputy Department Chair, Department of Bioinformatics and Computational Biology
The University of Texas MD Anderson Cancer Center
Faculty Member, Baylor College of Medicine
Houston, TX
MedicalResearch: What is the background for this study? What are the main findings?
Dr. Liang: An individual’s sex has been long recognized as a key factor affecting the risk of cancer development and management. However, previous studies on the sex effect have been limited to individual genes, single molecular data types, and single cancer lineages.
We performed a comprehensive analysis of molecular differences between male and female patients in a diversity of cancer types and revealed two sex-effect groups.
One group contains a small number of sex-affected genes, whereas the other shows much more extensive sex-biased molecular signatures. More than half of clinically actionable genes (e.g., therapeutic targets or biomarkers) show sex-biased signatures.
Dr. Serena Nik Zainal[/caption]
Serena Nik-Zainal MD PhD
Wellcome Beit Fellow & Honorary Consultant in Clinical Genetics
CDF Group Leader
Wellcome Trust Sanger Institute
United Kingdom
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Nik-Zainal: We have used the massive improvement in speed of "sequencing" (reading the human genetic material) in order to obtain comprehensive whole genome maps of 560 human breast cancer patients. This is the largest whole genome sequencing study of a single cancer type in the world. We wanted to forensically search these cancers, find all the important genes that drive breast cancer, find all the important mutation patterns that tell us something about why breast cells turn into cancer cells and then to pull it altogether for each patient. We wanted to be able to "profile" each cancer patient, to see if we could further our understanding of personal cancer genomes.
In all, we had 556 female and four male patients, and they were sought from all over the world – USA, Europe and Asia.
Wenpeng You[/caption]
Wenpeng You, PhD student
Biological Anthropology and Comparative Anatomy Research Unit
University of Adelaide | School of Medicine
Adelaide, Australia
[caption id="attachment_24262" align="alignleft" width="180"]
Dr. Maciej Henneberg[/caption]
Maciej Henneberg, PhD, DSc, FAIBiol
Wood Jones Professor of Anthropological and Comparative Anatomy
University of Adelaide School of Medicine;
Institute for Evolutionary Medicine, University of Zurich
Editor in Chief, Journal of Comparative Human Biology HOMO
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Type 1 diabetes disease has very strong genetic background. Prevalence of type 1 diabetes has been increasing globally. Previous studies focusing on regional genetics and environmental factors cannot fully explain this phenomenon. Due to insufficient medical knowledge up until early 20th century, people with type 1 diabetes disease would most commonly die during their teens or early 20s. Therefore, they did not have the opportunity to pass on their genes providing background for the development of type 1 diabetes to their next generations. Since discovery and introduction of insulin to modern medicine in early 1920s, more and more type 1 diabetes patients have been able to survive their reproduction cycle (up until and past 50 years of age). This has made more and more genes related to type 1 diabetes to accumulate in human populations.
We applied the Biological State Index which measures a probability to pass genes on to the next generation at population level. We found that the rapid increase in type 1 diabetes over the last few decades was correlated with increases of the Biological State Index and its proxy, human life expectancy, especially in more developed world in which natural selection has been relaxed most. This correlation was found after statistically excluding differences in countries income, levels of urbanization, sugar consumption and obesity prevalence.
Dr Lluís Ribas[/caption]
Lluís Ribas de Pouplana, Ph.D
IRB Barcelona
Barcelona 08028
MedicalResearch.com: What is the background for this study? What are the main findings?
Response: Ever since the discovery of the genetic code it became obvious that the system had not grown to its full theoretical potential of making proteins with 63 different amino acids.
Francis Crick called the code 'a frozen accident',
but it was unclear what had actually froze it.
In this article we offer an explanation to that, and we validate it experimentally.
What we find is that the central pieces of the genetic code, the transfer RNAs,
are unable to incorporate enough specific elements for the system to be able to
use 63 of them without confusion. Since you need a new tRNA for each new
amino acid, once the tRNA identification limit is reached you also reach the
maximum number of usable amino acids. This limit happened to be reached
at 20, and that's where it has stayed for 3 billion years.
Dr. Haidong Zhu[/caption]
Haidong Zhu, MD, PhD
Associate Professor of Pediatrics
Georgia Prevention Institute
Medical College of Georgia
Augusta University
MedicalResearch.com: What is the background for this study? What are the main findings?
Dr. Zhu: Vitamin D plays an important role in a wide range of body functions beyond bone health. Vitamin D deficiency is associated with increased risk of cancer and cardiovascular disease. Vitamin D deficiency is common among darker skin individuals, particularly African-Americans, which could contribute to health disparity. We want to understand underlying molecular mechanism (i.e. global DNA methylation) for how vitamin D deficiency causes cancer, cardiovascular disease and impaired immune function. DNA methylation, a chemical modification to our genome, is one of the ways that our body adapts to the environment. Low rate of global DNA methylation is a common event in cancer, which may lead to disturbances in the genome, make the genome more vulnerable to environmental damage and increase disease risk.
Our study shows that majority of black teens are vitamin D deficient and have a lower rate of global DNA methylation than white teens. We further demonstrate that vitamin D3 supplementation for 16 weeks increases global DNA methylation in black teens and young adults. Our study provides an important piece of evidence that vitamin D plays a role in epigenetic regulation in humans, which could be an underlying mechanism for vitamin D-deficiency related disease risk and health disparity.
