(Press-News.org) Scientists at The Children's Hospital of Philadelphia have identified both common and rare gene variants associated with the eating disorder anorexia nervosa. In the largest genetic study of this psychiatric disorder, the researchers found intriguing clues to genes they are subjecting to further investigation, including genes active in neuronal signaling and in shaping interconnections among brain cells.
Anorexia nervosa (AN) affects an estimated 9 in 1000 women in the United States. Patients have food refusal, weight loss, an irrational fear of weight gain even when emaciated, and distorted self-image of body weight and shape.
Women are affected 10 times more frequently than men, with the disorder nearly always beginning during adolescence. AN has the highest mortality rate of all psychiatric disorders, and successful treatment is challenging.
Twin studies and other family studies have suggested that AN is strongly heritable. "However, despite various genetic studies that identified a handful of candidate genes associated with AN, the genetic architecture underlying susceptibility to AN has been largely unknown," said study leader Hakon Hakonarson, M.D., Ph.D., director of the Center for Applied Genomics at The Children's Hospital of Philadelphia. The research appeared online in Molecular Psychiatry on Nov. 16.
"This is the first genome-wide association study on a large anorexia cohort, as well as the first study of copy number variations in the disorder," said Hakonarson. Genome-wide association studies (GWAS) search for single-nucleotide polymorphisms, or SNPs—common gene variants that typically act as pointers to a gene region with a small effect on raising disease risk. The study team also performed a parallel search for copy number variations (CNVs), rarer variants that usually have a stronger impact on disease risk.
The sample size was the largest used in an AN gene study—DNA came from 1,003 AN patients, all but 24 of them female, from various sources, having an average age of 27 years. For comparison, there was a control group of 3,733 pediatric subjects (average age of 13), drawn from the Children's Hospital pediatric network.
"We confirmed results of previous studies of anorexia nervosa: SNPs in the gene OPRD1 and near the gene HTR1D confer risk for the disease," said Hakonarson. "We did not detect other obvious candidate genes, but we did generate a list of other genes that we are analyzing in follow-up studies." One SNP is between the CHD10 and CHD9 genes, a region that Hakonarson associated with autism spectrum disorders in 2009. Called cadherin genes, CHD10 and CHD9 code for neuronal cell-adhesion molecules—proteins that influence how neurons communicate with each other in the brain.
The current anorexia study also investigated CNVs—deletions or duplications of DNA sequences. Previous research by Hakonarson and others has shown that CNVs play a significant role in other neuropsychiatric disorders, such as schizophrenia, bipolar disorder and autism.
The current study suggests that CNVs may play a less important role in anorexia than they do in schizophrenia and autism. Nonetheless, the researchers identified several rare CNVs that occurred only in AN cases, including a deletion of DNA on a region of chromosome 13.
"Our study suggests that both common SNPs and rare CNVs contribute to the pathogenesis of anorexia nervosa," said Hakonarson. "The gene variants we discovered are worthy of further analysis in independent cohorts. However, the relatively modest number of anorexia cases explained by these results we found suggests that many other candidate genes remain unknown. Future studies will require much larger sample sizes to detect additional gene variants involved in this complex disorder."
INFORMATION:
Support for this research came from an Institute Development Award from The Children's Hospital of Philadelphia, as well as from the Price Foundation, the Klarman Family Foundation, and the Scripps Translational Science Institute of La Jolla, Calif. Hakonarson's co-authors were from the University of Pennsylvania, the Scripps Translational Science Institute, the Scripps Research Institute, the University of California, San Diego, and the Price Foundation Collaborative Group.
K. Wang et al, "A Genome-wide Association Study on Common SNPs and Rare CNVs in Anorexia Nervosa," Molecular Psychiatry, published online Nov. 16, 2010. doi:10.1038/mp.2010.107
About The Children's Hospital of Philadelphia: The Children's Hospital of Philadelphia was founded in 1855 as the nation's first pediatric hospital. Through its long-standing commitment to providing exceptional patient care, training new generations of pediatric healthcare professionals and pioneering major research initiatives, Children's Hospital has fostered many discoveries that have benefited children worldwide. Its pediatric research program is among the largest in the country, ranking third in National Institutes of Health funding. In addition, its unique family-centered care and public service programs have brought the 460-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.
Gene links to anorexia found by Children's Hospital of Philadelphia researchers
Largest genetic study of the eating disorder detects common and rare variants
2010-11-20
ELSE PRESS RELEASES FROM THIS DATE:
Designing more effective anti-HIV antibodies
2010-11-20
Boston, Mass. – Although people infected with HIV produce many antibodies against the protein encapsulating the virus, most of these antibodies are strangely ineffective at fighting the disease. A new study suggests why some of the most common of these antibodies don't work: they target the protein in a form it takes after the virus has already invaded the cell, when it's too late, report researchers at Children's Hospital Boston and their colleagues.
The findings, published online Nov. 14 in the journal Nature Structural & Molecular Biology, refocus attention on the ...
Professor Zvi Ram presents phase III recurrent glioblastoma survival and quality of life data from the first pivotal study of the NovoTTF-100A at 15th Annual Society for Neuro-Oncology Scientific Meet
2010-11-20
MONTREAL, CANADA - November 19, 2010 - Data presented today from a pivotal, phase III randomized clinical trial for patients with recurrent glioblastoma tumors suggest that Tumor Treating Fields (TTF) therapy may increase median survival time and improve quality of life scores compared to best standard of care chemotherapy. Professor Zvi Ram, chairman of the Department of Neurosurgery at Tel-Aviv Sourasky Medical Center, presented the data at the Society for Neuro-Oncology (SNO) Annual Scientific Meeting.
Physicians delivered the investigational TTF therapy to patients ...
Childhood obesity linked to increased risk of adult cardiovascular and metabolic disorders
2010-11-20
New Rochelle, NY, November 19, 2010—Mounting evidence linking childhood obesity to an increasing risk of obesity, heart disease, type 2 diabetes, and other cardiovascular and metabolic disorders in adulthood is clearly presented in a comprehensive review article in the current issue of Childhood Obesity, published by Mary Ann Liebert, Inc. The article is available free online.
Authors Megan Moriarty-Kelsey, MD and Stephen Daniels, MD, PhD, Department of Pediatrics, University of Colorado School of Medicine, caution that the rising prevalence of obesity in children will ...
New path for colon cancer drug discovery
2010-11-20
An old pinworm medicine is a new lead in the search for compounds that block a signaling pathway implicated in colon cancer. The findings, reported by Vanderbilt University Medical Center researchers in the November issue of Nature Chemical Biology, suggest a fresh approach for developing therapeutics that target the pathway.
More than 90 percent of sporadic (non-inherited) colon cancers – the second deadliest type of cancer in the developed world – are caused by mutations that result in inappropriate activation of the Wnt (pronounced "wint") signaling pathway. Blocking ...
Scripps Research scientists identify first synthetic activator of 2 critical proteins
2010-11-20
JUPITER, FL, November 19, 2010 – Scientists from the Florida campus of The Scripps Research Institute have identified a novel synthetic activator of a pair of proteins that belong to a protein family playing key roles in human metabolism and immune function. The discovery could provide new and potentially more effective therapeutic approaches to diseases ranging from diabetes to osteoporosis.
The study was published in the November issue (Volume 5, Issue 11) of the journal ACS Chemical Biology.
"This new compound is particularly important because it works in vivo, ...
Invention helps students learn surgical techniques before operating on patients
2010-11-20
FORT COLLINS - In the last 50 years, modern medicine has made astounding advances in surgery, yet many of today's veterinary and human medicine students still hone basic surgical and suturing skills on carpet pads and pig's feet before transitioning to a live patient. An invention by Colorado State University veterinarians provides students with artificial body parts that look, feel, behave, and even bleed just like real skin, muscles and vessels.
The artificial replicas of sections of human and animal bodies -- such as an abdominal wall -- give students a realistic learning ...
UH physicists study behavior of enzyme linked to Alzheimer's, cancer
2010-11-20
HOUSTON, Nov. 19, 2010 – University of Houston (UH) physicists are using complex computer simulations to illuminate the workings of a crucial protein that, when malfunctioning, may cause Alzheimer's and cancer.
Margaret Cheung, assistant professor of physics at UH, and Antonios Samiotakis, a physics Ph.D. student, described their findings in a paper titled "Structure, function, and folding of phosphoglycerate kinase (PGK) are strongly perturbed by macromolecular crowding," published in a recent issue of the journal Proceedings of the National Academy of Sciences, one ...
New study into bladder regeneration heralds organ replacement treatment
2010-11-20
Researchers in the United States have developed a medical model for regenerating bladders using stem cells harvested from a patient's own bone marrow. The research, published in STEM CELLS, is especially relevant for paediatric patients suffering from abnormally developed bladders, but also represents another step towards new organ replacement therapies.
The research, led by Dr Arun Sharma and Earl Cheng from the Feinberg School of Medicine at Northwestern University and Children's Memorial Research Center, focused on bone marrow mesenchymal stem cells (MSCs) taken from ...
Busy microbial world discovered in deepest ocean crust ever explored
2010-11-20
CORVALLIS, Ore. – The first study to ever explore biological activity in the deepest layer of ocean crust has found bacteria with a remarkable range of capabilities, including eating hydrocarbons and natural gas, and "fixing" or storing carbon.
The research, just published in the journal PLoS One, showed that a significant number and amount of bacterial forms were present, even in temperatures near the boiling point of water.
"This is a new ecosystem that almost no one has ever explored," said Martin Fisk, a professor in the College of Oceanic and Atmospheric Sciences ...
AgriLife scientist: Functional amino acids regulate key metabolic pathways
2010-11-20
COLLEGE STATION - Functional amino acids play a critical role in the development of both animals and humans, according to a Texas AgriLife Research scientist.
In a journal article appearing in the American Society for Nutrition (Advances in Nutrition 1:31-37, 2010), Dr. Guoyao Wu, AgriLife Research animal nutritionist and senior faculty fellow in the department of animal science at Texas A&M University, calls for scientists to "think out of the box" and place more emphasis on this area of study.
"We need to move forward and capitalize on the potential of functional ...
LAST 30 PRESS RELEASES:
Time alone heightens ‘threat alert’ in teenagers – even when connecting on social media
Study challenges long-held theories on how migratory birds navigate
Unlocking the secrets of ketosis
AI analysis of PET/CT images can predict side effects of immunotherapy in lung cancer
Making an impact. Research studies a new side of helmet safety: faceguard failures
Specific long term condition combinations have major role in NHS ‘winter pressures’
Men often struggle with transition to fatherhood amid lack of targeted information and support
More green space linked to fewer preventable deaths in most deprived areas of UK
Immunotherapy drug pembrolizumab improves outcomes for patients with soft tissue sarcoma
A formula for life? New model calculates chances of intelligent beings in our Universe and beyond
Could a genetic flaw be the key to stopping people craving sugary treats?
Experts urge complex systems approach to assess A.I. risks
Fossil fuel CO2 emissions increase again in 2024
Winners of Applied Microbiology International Horizon Awards 2024 announced
A toolkit for unraveling the links between intimate partner violence, trauma and substance misuse
Can everyday physical activity improve cognitive health in middle age?
Updated guidance reaffirms CPR with breaths essential for cardiac arrest following drowning
Study reveals medical boards rarely discipline physician misinformation
New treatment helps children with rare spinal condition regain ability to walk
'Grow Your Own' teacher prep pipeline at the University of Louisiana at Lafayette funded by US Department of Education
Lab-grown human immune system uncovers weakened response in cancer patients
More than 5 million Americans would be eligible for psychedelic therapy, study finds
Children’s Hospital of Philadelphia researchers find community health workers play critical role in coordinating asthma care across home, school and community
Comprehensive Genomic Profiling leads to better patient outcomes, new joint study says
Animated movie characters with strabismus are more likely to be villains, study finds
How retailers change ordering strategy when a supplier starts its own direct channel
Young coral use metabolic tricks to resist bleaching
Protecting tax whistleblowers pays off
Bioluminescent proteins made from scratch enable non-invasive, multi-functional biological imaging
New study links air pollution with higher rates of head and neck cancer
[Press-News.org] Gene links to anorexia found by Children's Hospital of Philadelphia researchersLargest genetic study of the eating disorder detects common and rare variants