The Genetics of Obesity and Related Traits Program
At the Icahn School of Medicine at Mount Sinai
Genetic variations that cause obesity help us gain insight into the biology that regulates body weight.
It is not just diet and physical activity; also your genes determine how easily you gain or lose weight. Around 40-70% of all the inter-individual variation in body weight is due to the fact that people differ genetically.
We aim to identify genes that cause obesity to gain insight in the biological pathways through which these genes and their proteins control body weight. Insight in the genetics of obesity means insight in its underlying biology.
Over the past decade, genome-wide screens for obesity have identified hundreds of genetic variations that point to the brain as a key organ in the control of body weight regulation, which is consistent with observations from monogenic cases of extreme and early onset obesity.
A major challenge in the field is translation of these loci into “tangible” genes that can be studied in more experimental settings to get to the bottom of their biology. We try to close the gap between gene discovery and functional follow-up by focusing on more refined phenotypes, such as body fat percentage, specific adipose depots, and biomarkers, and on variants with a high potential to disrupt gene function.
It is only once causal genes are identified that we can start thinking about therapeutics, and this requires geneticists and physiologists to work together even more than before. Therefore, we are always on the look out to collaborate with researchers who have complementary expertise to solve the obesity puzzle.
I grew up in a small town in Belgium. I love(d) being active, so after high school, I decided to study Kinesiology (BSc, MSc) and Education (MEd) to become a PhysEd teacher. I soon realized, though, that my true interest was more in public health research. Hence, I continued my graduate studies and obtained a PhD in Medical Science (Epidemiology) at the University of Leuven (Belgium) in 2001, on the fetal origins of adult disease using a twin design.
An award of the Belgian American Educational Foundation allowed me to do a postdoctoral fellowship at the Pennington Biomedical Research Center in Baton Rouge (LA, USA), in Dr Claude Bouchard’s Human Genetics lab, where I aimed to identify genes for energy expenditure and fat oxidation through linkage and association studies.
After my postdoc, in July 2005, I moved to the UK and joined the MRC Epidemiology Unit in Cambridge to become Group Leader of the Genetic Aetiology of Obesity Programme.
In December 2011, I returned to the US to join the Charles Bronfman Institute for Personalized Medicine at the Icahn School of Medicine at Mount Sinai, where I am a tenured Professor, leading the Genetics of Obesity and Related Metabolic Traits Program. I am also a co-Director of the Charles Bronfman Institute for Personalized Medicine and co-ordinate numerous scientific collaborations that involve Mount Sinai's BioMe Biobank.
I have never stopped loving being physically active, though. These days, you can find me running every morning in Central Park.
I received my PhD in Biomedial Sciences from the University of Montréal, Canada under the supervision of Dr. Guillaume Lettre. My research focused on gene discovery in both rare disease and complex traits. In particular, I was interested in finding novel genetic mutations that cause familial cardiomyopathies in French Canadians using next generation exome sequencing, as well as identifying genes that modify disease severity within and across families. My work on complex traits mainly involved leading a large-scale association analysis effort for gene discovery in blood cell traits through the Blood Cell Consortium. Prior to my PhD, I completed a Master’s degree in Human Genetics at McGill University, Canada and a Bachelor of Science in Biomathematics from the same institution.
I joined the Loos lab as a postdoctoral fellow in September 2017. I am working on gene discovery in obesity and cardio-metabolic traits using whole exome and whole genome sequencing data in collaboration with the TopMed program. I am also interested to characterize obesity-associated variants and attempt to identify actionable loci. Another research interest of mine is dissecting the genetic determinants of “healthy obesity” by studying individuals that are obese yet metabolically healthy using the Electronic Medical Records (EMR) data at Mount Sinai (BioMe).
I was born in a small town in southern Brazil, and since I remember, always wanted to pursue a career in science. I was awarded a scholarship for a BsC in Computer Science at University of Passo Fundo (Brazil) for good grades during my secondary education. I was then awarded another scholarship to pursue my MSc in Computer Science at the Pontifical Catholic University of Porto Alegre (Brazil) and University of Trento (Italy).
After training and research in data mining and machine learning, I decided to apply my computational knowledge to public health research. I wrote a project and was awarded a third scholarship, this time for a PhD in Genetics and Bioinformatics at the University Medical Center Utrecht (The Netherlands). There, I found my real passion in integrating genome, regulome and transcriptome information to facilitate the understanding of biological mechanisms affected by such genetic variation, and identification of drug targets for better prevention and treatment of complex diseases.
I joined the Loos Lab by the end of 2018, where I currently work on integrative approaches for fine-mapping and functional annotation to undercover the epigenetic mechanisms of obesity and related metabolic traits. Outside of the office, I can likely be found putting into practice my other two passions: jazz and lindy hop dancing, and reading everything I can.
I studied Medical Informatics with major in statistics at the University of Heidelberg in Germany and later completed a PhD (Dr. rer. nat.) in Bioinformatics at the Institute of Biometry and Statistics at the University of Luebeck. During this time, I was an analyst on several projects involving the GIANT and CARDIoGRAM consortia.
I have also collaborated with the German Neonatal Network (GNN), where I maintained and analyzed genotype data and conducted epidemiological studies involving very low birth weight (VLBW) newborns.
I joined the Loos Lab as a postdoctoral fellow in 2016 and am primarily interested in analyzing an interpreting genetic data from the Mount Sinai BioMe Biobank and UK Biobank with newly developed methods. I also contributes to the PAGE Annotation Group, which has the aim to consolidate annotation-databases, to assure the quality and to simplify the variant annotation for sequencing data.
After obtaining my medical degree from Leiden University, I started as a PhD student at the Leiden University Medical Center (LUMC), focusing on methodological and genetic aspects of (research into) statin treatment. During the same period I was accepted to the nationally accredited SMBWO Epidemiology B training program, which allowed me to further develop my interests in research methodology and teaching.
In 2017 I was awarded the Young Talent funding by the ENERGISE consortium (primary applicant: Dr ir. Renée de Mutsert). Alongside my recent research activities I worked as a teaching fellow to co-develop a Coursera-based MOOC (Population Health: Study Design) for the upcoming Population Health Management Master of the LUMC-Campus The Hague.
During the final phases of submitting my PhD dissertation, which I defended in April 2019, I was awarded the NWO/ZonMW Rubicon grant. This grant will enable me to gain research experience in the Loos Lab during a period of two years, working on resilience to obesity in genetically at-risk individuals.
Lauren Stalbow, MD-PhD Student
Growing up in an NYC suburb, I originally wanted to pursue a career in art history. Due to happenstance I studied neuroscience at the Macaulay Honors College at Queens College. I began researching the molecular pathways associated with chronic neuronal inflammation. For this I was awarded the Barry M. Goldwater Scholarship in 2014.
Upon graduation, I worked for two years at the Rockefeller University studying neuronal differentiation in a stem cell model.
My interests in obesity studies developed after starting in the MD-PhD program and learning about the harmful effects obesity has on patients as well as the heavy burden that it places on our healthcare system. Given the rising prevalence of obesity, I shifted my research interests to address this pressing concern.
When not working, I can be found baking sourdough, riding on my homemade Peloton bike, travelling to some remote country, or deconstructing the usage of chiaroscuro in Caravaggio’s paintings.
I received a BSc in Marine Biology from the University of California, Santa Cruz in 2001, and then spent 7 years as a professional chef in both San Francisco and New York City prior to earning his MSc in Applied Physiology and Nutrition from Teachers College, Columbia University in 2008 while working as both an Exercise Physiologist and Research Coordinator for the New York Obesity Research Center at St. Luke’s-Roosevelt Hospital. Before joining MSSM, I obtained my PhD in Integrative Biology of Disease from the Keck School of Medicine at USC, where I obtained complimentary expertise in clinical and genetic obesity investigation and researched the effects of dietary and genetic factors on nonalcoholic fatty liver disease in Hispanic youth.
My current work involves better understanding the early establishment of the fetal gut microbiota and the role of the microbiome in the etiology of obesity and related diseases. The aim of this work is to 1. identify mediators of the gut bacterial population so as to establish targets for interventions to improve health outcomes and 2. to unravel cause vs. consequence in the relationships between diet, microbiome and host health.
Outside of the lab, I am a former professional chef and an accomplished athlete. I have worked in top level restaurants in San Francisco and NYC and was a member of Team USA Triathlon in 2008.
I graduated with a Bachelor of Medicine degree from Peking University Health Science Center, Beijing, China and a BSc in Psychology from Peking University in 2012. However, I then realized that I was more interested in public health research, rather than clinics. Thus, I decided to study Nutrition and Health at Wageningen University, the Netherlands and received my MSc specialized in Epidemiology and Public Health.
In 2014, I moved to the United States and continued my graduate training in Epidemiology at the University of Texas Health Science Center at Houston, TX, under the supervision of Dr. Eric Boerwinkle. My PhD research focused on integrating genomics, metabolomics and environmental factors together to facilitate the understanding of complex traits like cardiovascular disease and related cardio-metabolic traits. I was interested in applying novel statistical methods to reveal the role of gene-environment interactions in the context of rare genetic variants. I led and collaborated as an analyst for several large-scale genetic association analysis projects in the Cohorts for Heart and Aging Research in Genomic Epidemiology (CHARGE) consortium. When I was not wearing my human genetics hat, my work involved epidemiology studies in metabolomics- another ‘-omics’ science, and the goal was to discover novel biomarkers, as well as to better understand the etiology of complex diseases.
I joined the Loos lab as a postdoctoral fellow at the beginning of 2019. I started working on biobank scale data like BioMe and UK Biobank, and obesity related traits, such as physical activity, body mass index and metabolically healthy obesity.
Besides work, I am obsessed with good food, always on the hunt for the very best restaurants.
What We Do
Our primary research interests focus on the identification of genes and genetic loci contributing to the risk of obesity and related metabolic traits. We have been involved in gene discovery since 2005, when ‘genome - wide association’ was introduced and have since actively contributed to many consortia that use this approach to identify genetic loci for a large number of metabolic traits.
By identifying genes that influence the risk of obesity and related metabolic traits, we aim to provide new insights in the mechanisms that regulate body weight and risk of metabolic disease. Eventually, such biological insights might results in a better tailored treatment or prevention.
Increasingly, our gene discovery work also focuses on rare and low frequency variants from whole genome sequencing (N~12,000) and whole exome sequencing (N~32,000) projects in individuals of diverse ancestry.
We have established consortia to study the genetics of body fat percentage, leptin levels, and physical activity; i.e. phenotypes that target different components of the obesity etiology.
We are actively involved in the GIANT (Genetic Investigation of ANthropometric Traits) Consortium, lead by Prof. Joel Hirschhorn, with whom we have discovered many common, low frequency and rare variants associated with BMI and WHR, and height.
Genes and environments interact
Even though obesity is heritable, changes in our environment have fueled the epidemic over the past three decades. Yet, not everyone gains weight in the current obesogenic environment; responses to the environment depends at least in part on a person’s genetic susceptibility.
We aim to examine how lifestyle influences people’s genetic susceptibility to obesity and related diseases. We study these interactions between genes and lifestyle through following up on established diseases-associated genetic loci, as well as through screening the whole genome.
For example, we have shown that a genetic susceptibility to obesity is attenuated by ~30% in physically active individuals.
Ancestrally diverse populations
Differences in disease burden between ancestrally diverse populations are a major cause of health disparities in the United States, generally affecting racial and ethnic minorities the most. While lifestyle, cultural values, health care access and socioeconomic status are undeniably important contributors to the disproportionate disease burden, genetic variation between ancestrally diverse populations may contribute as well.
Through our participation in the the PAGE (Population Architecture using Genomics and Epidemiology) study, we examine disease-associated loci across ancestries and assess their generalizability or ancestry-specificity.
By understanding these genetic factors that contribute to population’s disease susceptibility, health disparities can be reduced by tailoring prevention and personalizing treatment for specific subgroups.
The Mount Sinai BioMe Biobank
Our main resource for our studies is Mount Sinai's BioMe Biobank, an electronic health record (EHR)-linked clinical care Biobank and comprises >40,000 participants from diverse ancestries, characterized by a broad spectrum of longitudinal biomedical traits.
Enrolled participants consent to be followed throughout their clinical care (past, present, and future) in real-time, allowing us to integrate their genomic information with their EHRs for discovery research and clinical care implementation. BioMe participants consent for recall, based on their genotype and/or phenotype, permitting in-depth follow-up and functional studies for selected participants at any time.
BioMe comprises a strong representation of minority populations that hitherto have been largely underrepresented in studies of the genetic architecture of common disease. Specifically, BioMe participants are of African (24%), Hispanic/Latino (35%), European (32%) and other/mixed ancestry. With this broad ancestral diversity, BioMe is uniquely positioned to examine the impact of demographic and evolutionary forces that have shaped common disease risk.
Genotype data is available for more than 30,000 participants, including whole genome sequencing (N~12,000), whole exome sequencing (N~32,000) and genome-wide (exome) arrays (N~32,000).
With data from the Mount Sinai BioMe Biobank, we participate in a large number of consortia.