Children who have older siblings or frequent interaction with grandparents are diagnosed with autism spectrum disorders (ASD) earlier than those who do not, according to new research conducted at the Seaver Autism Center for Research and Treatment at Mount Sinai, and published in the journal Autism.
The study, titled “Grandma Knows Best: Family Structure and Age of Diagnosis of Autism Spectrum Disorder,” found that about 50 percent of friends and family members reported they had suspected a child to have a serious condition before they were aware that either parent was concerned. Maternal grandmothers and teachers were the two most common relationship categories to first raise concerns. “Our work shows the important role that family members and friends can play in the timing of a child’s initial diagnosis of autism,” says Joseph D. Buxbaum, PhD, the G. Harold and Leila Y. Mathers Research Professor, and Professor of Psychiatry, Genetics and Genomic Sciences, and Neuroscience, Icahn School of Medicine at Mount Sinai, and Director of the Seaver Autism Center. He is senior author of the paper, which was published online February 8, 2017. The study included colleagues at Columbia Business School and Carnegie Mellon University.
The team conducted an online survey of 477 parents of children with autism. In addition, they carried out novel, follow-up surveys with 196 “friends and family,” who were referred by parents. Eighty percent of the children with ASD were boys, and the median age of diagnosis was 33 months. Frequent interaction with a grandmother reduced the age of diagnosis by 5.18 months, and frequent interaction with a grandfather reduced the age of diagnosis by 3.78 months. “Since early detection of ASD is critical to effective treatment interventions, we hope the study will serve as a call to action to encourage family and friends to share concerns early on,” Dr. Buxbaum says.
In other news, the Autism Sequencing Consortium, a multi-institute research group founded by Dr. Buxbaum, has received a $7 million extension of a grant from the National Institutes of Health to collect, analyze, and share samples and genetic data from people diagnosed with autism.
The Consortium now includes more than 40 international groups and 150 researchers who have generated gene sequencing data from 29,000 individuals, making it the largest such study to date in autism. All shared data and analyses are hosted on a supercomputer called Minerva, designed by Mount Sinai faculty, which enables joint analysis of largescale data. The new grant will extend the project through 2022 and expand the sample to include more than 50,000 individuals.
As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers at the Icahn School of Medicine at Mount Sinai have found. Their study, published in the journal Science, may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America.
Zahi A. Fayad, PhD, Mount Sinai Endowed Chair in Medical Imaging and Bioengineering, Professor of Radiology and Medicine (Cardiology), and Director of the Translational and Molecular Imaging Institute (TMII) at the Icahn School of Medicine at Mount Sinai, and the Principal Investigator of the study
Researchers at the Icahn School of Medicine at Mount Sinai have been awarded $13 million from the National Heart, Lung, and Blood Institute of the National Institutes of Health (NIH) for a five-year research program that aims to uncover the mechanisms by which stress contributes to cardiovascular risk. The program aims to improve our understanding of how the effect of stress on the brain can directly impact the immune system and cardiovascular disease, and to provide a scientific platform for clinicians and researchers to integrate this knowledge into patient care.
REVEL developers Weiva Sieh, MD, PhD, left, and Joseph Rothstein, MS
Sequencing-based genetic tests are making personalized medicine a reality for patients who carry certain mutations for serious diseases, including breast and prostate cancer. Armed with information about the pathogenicity of such variants in their genome, these patients can now make proactive decisions about their health care early enough to increase the odds of success in preventing or treating disease.
But for each step forward in this new frontier of personalized medicine, physicians and scientists are stymied by their lack of knowledge about thousands of other rare variants in a patient’s genome that could also portend disease. For this reason, two researchers at the Icahn School of Medicine at Mount Sinai developed REVEL, a novel tool designed to make sense of these variants of unknown importance in order to help guide patient care and risk management and to facilitate research.
Developed by Weiva Sieh, MD, PhD, Associate Professor of Population Health Science and Policy, and Genetics and Genomic Sciences; and Joseph Rothstein, MS, an Instructor of Genetics and Genomic Sciences, and Population Health Science and Policy, REVEL is an acronym for Rare Exome Variant Ensemble Learner. The tool predicts the likelihood of whether a particular coding variant in a person’s genome is disease-causing or benign.
“REVEL is timely and significant because the number of rare variants discovered by sequencing studies is vast and growing and little is known regarding their function,” says Dr. Sieh. “Yet few pathogenicity prediction tools have targeted rare missense variants, leaving researchers and clinicians to struggle with their interpretation.” The ability to distinguish among the approximately 10,000 missense variants in each person’s genome that result in protein changes that could potentially be harmful also helps researchers set priorities for the variants they may wish to study further as new disease-causing genes. Identifying more of these variants would enable personalized medicine to realize its potential in helping more patients benefit from prevention and treatment regimens tailored to their individual disease risks.
Other tools that use different predictive features do exist, but they often do not agree with each other on the likelihood of pathogenicity. Dr. Sieh and Mr. Rothstein created REVEL as an ensemble method that uses machine learning to combine information from many of these other tools in order to generate a consensus score. REVEL incorporates 18 pathogenicity prediction scores from 13 tools, and it specializes in prioritizing the most clinically or functionally relevant variants among the sea of rare variants that are being discovered through next-generation sequencing.
The Icahn School of Medicine at Mount Sinai is establishing the Institute for Exposomic Research under the leadership of Robert O. Wright, MD, MPH, and Rosalind J. Wright, MD, MPH, two international leaders in environmental health. The Institute, the first in the world focused on exposomics, will study the effects of environmental exposures on health and will translate these findings into new strategies for prevention and treatment.
“The exposome is a new research field and is analogous to genomics,” says Dr. Robert Wright, Ethel H. Wise Professor and Chair, Department of Environmental Medicine and Public Health, and Director, Senator Frank R. Lautenberg Environmental Health Sciences Laboratory. “While genomics concerns all the genetic factors that predict health, the exposome encompasses all the environmental factors that affect your health, including nutrition, social factors, chemicals, and the physical environment, from the time you are conceived until the time you die. To understand health, you must understand both fields.” He is Director of the Institute, and its Co-Director is Dr. Rosalind Wright, Horace W. Goldsmith Professor in Children’s Health Research and Dean of Translational Biomedical Sciences at the Icahn School of Medicine.
Robert O. Wright, MD, MPH
The Institute will build upon the expertise of the Lautenberg Laboratory to develop new technologies and methodologies in exposomics. Mount Sinai’s recent investment in the field has already led to significant funding from the National Institutes of Health (NIH), including a $9 million grant in December for Environmental influences on Child Health Outcomes (ECHO), to investigate the effects of a broad range of environmental exposures on children’s long-term health, and two additional $10 million NIH grants for the Children’s Health Exposure Analysis Resource (CHEAR) program. CHEAR provides laboratory resources to measure environmental chemicals, metabolites, hormones, and other factors representing components of the human exposome. The CHEAR grants also fund a Data Repository, Analysis, and Science Center, led by Susan L. Teitelbaum, PhD, Professor of Environmental Medicine and Public Health, that specializes in analyzing exposomic big data.
A major part of the CHEAR facilities’ mission will be analyzing the samples collected by ECHO, a seven-year study of 50,000 children followed longitudinally across the United States. Mount Sinai is part of a consortium that includes programs in Boston and Virginia and will recruit 5,000 of these subjects. The Wrights are part of the committees now setting up protocols for the national ECHO study.
The doctors have been collaborating for more than 20 years. They first met in medical school at the University of Michigan. Rosalind Wright specialized in critical care and adult pulmonary medicine and Robert Wright in medical toxicology and pediatric emergency medicine. Over the years their interests converged, in large part because they were both concerned by the environmental issues that brought their patients to the hospital. “For me it became an issue of prevention,” Dr. Rosalind Wright says. “Taking care of someone with very advanced, end-stage lung disease, I could adjust medications so the patient could walk a little farther or sleep a little better. But I thought, ‘Where do we start so that we can give people a healthier life overall, as well as help them live longer?’ Getting them to stop smoking, for example, has a small effect. But if we go back to the root of the unhealthy trends, we can have a huge impact. For example, I was struck by the data showing that if a mother smokes during pregnancy or she experiences high stress in pregnancy, the child will have decreased lung function by age 6 or 7, and that lower lung function will track over their life and make them more likely to develop chronic lung disease.”
The new Institute will expand exposomics into research programs in disciplines across campus, including personalized medicine, cancer, women’s health, aging, immunology, and clinical trials. “Intuitively, we all know that our environment plays the major role in shaping our health, but until recently the tools to measure environment on an ‘omic’ scale didn’t exist. That’s the future, and it aligns with the changes happening in health care,” Dr. Robert Wright says. “As Mount Sinai’s leadership says, population health, not fee for service, is the future, and that means prevention. Investing in understanding exposomics will give us the tools for prevention.”
Peter Palese, PhD, chair of the department of microbiology at the Icahn School of Medicine at Mount Sinai, discusses the microbiology of flu vaccination and his work on a universal flu vaccine.
“In the U.S. alone every year, estimates are that between 30,000 and 50,000 people die of influenza despite the availability of the vaccine. The ideal vaccine would be one which is given once in a lifetime, and it would provide protection against all influenza strains. We hope that we will achieve the same with our universal influenza vaccine, which we are developing at Mount Sinai.”
As the Zika virus continues to spread rapidly across the globe, it might pose a particular risk to people previously infected with two related viruses, dengue and West Nile, researchers at the Icahn School of Medicine at Mount Sinai have found. Their study, published in the journal Science, may help explain the severe manifestations of Zika virus infection observed in specific populations, including those in South America.
