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Archive - Apr 7, 2013


Massive Study Reveals New Genes for Height and Obesity

An international research team has identified seven new gene loci linked to obesity. Researchers were also able to show that the genetic mechanisms that cause extreme obesity are similar to those that cause milder forms of overweight and obesity. The scientists were also able to identify four new gene loci for height. A total of more than 260,000 people were included in the study of the links between genes and obesity, which was published online on April 7, 2013 in Nature Genetics. The aim of the study was to identify new genes that increase the risk of obesity, but also to compare genetic factors that cause extreme obesity with those that are linked to rest of the body mass index (BMI) range. "We know from experience that genetic factors are important for the emergence of both milder and more extreme forms of obesity, but how much overlap there is between genes that are involved in extreme obesity and normal or slightly elevated BMI has not been examined systematically previously," says Dr. Erik Ingelsson, Professor at the Department of Medical Sciences and Science for Life Laboratory, Uppsala University, who coordinated the study. The researchers studied gene variants, or positions in the genetic code that differ between individuals. Many million such commonly occurring inherited differences are scattered throughout the genome. In the just published study, researchers identified loci (regions of the genome) that are linked to obesity through examining the relationship between different body measurements and 2.8 million gene variants in 168,267 participants. The scientists then carried out a targeted follow-up of the 273 gene variants with the strongest link to various body measurements in another 109,703 people.

Seven New Loci Associated with Age-Related Macular Degeneration

Genetic variants associated with age-related macular degeneration (AMD) are reported in a study published online on March 3, 2013 in Nature Genetics. AMD is a common cause of blindness and visual impairment in older adults. Dr. Gonçalo Abecasis and colleagues report a meta-analysis of genome-wide association studies for AMD, including over 17,100 individuals with advanced disease and over 60,000 healthy controls. This included 18 international studies from the AMD Gene Consortium. The researchers identified seven genomic regions newly associated with AMD risk, and 19 associated regions overall. Their analyses across studies including populations of European and Asian ancestry provide insight into differential associations across ancestry. The authors suggest that pathways in complement activity, lipid metabolism, and extracellular matrix remodeling and angiogenesis are involved in the development of AMD. [Press release] [Nature Genetics abstract]

Four Genes Newly Associated with Severe Childhood Obesity

Researchers have identified four genes newly associated with severe childhood obesity. They also found an increased burden of rare structural variations in severely obese children. The new work was reported online on April 7, 2013 in Nature Genetics. The research team found that structural variations can delete sections of DNA that help to maintain protein receptors known to be involved in the regulation of weight. These receptors are promising targets for the development of new drugs against obesity. As one of the major health issues affecting modern societies, obesity has increasingly received public attention. Genes, behavior, and environment, all contribute to the development of obesity. Children with severe obesity are more likely to have a strong genetic contribution. This study has enhanced understanding of how both common and rare variants around specific genes and genetic regions are involved in severe childhood obesity. “We’ve known for a long time that changes to our genes can increase our risk of obesity. For example, the gene FTO has been unequivocally associated with body-mass index (BMI), obesity, and other obesity-related traits,” says Dr. Eleanor Wheeler, first author from the Wellcome Trust Sanger Institute. “In our study of severely obese children, we found that variations in or near two of the newly associated genes seem to have a comparable or greater effect on obesity than the FTO gene: PRKCH and RMST.” The team found that different genes can be involved in severe childhood obesity compared to obesity in adults. Rare genetic changes in one of the newly associated genes, LEPR, are known to cause a severe form of early-onset obesity. The team identified a more common variant in this gene, found in 6 per cent of the population, that can increase a person’s risk of obesity.

New Blood Test Provides Fuller Picture of Cancer Mutations Than Biopsies

A new blood test revealed more of the gene mutations that sustain certain digestive-tract tumors than did a DNA analysis of a traditional tumor biopsy, Dana-Farber Cancer Institute investigators reported in an April 6, 2013 press conference at the American Association for Cancer Research (AACR) annual meeting in Washington, D.C., April 6-10, 2013. The findings (Abstract LB-295) will also be released in an oral presentation on Tuesday, April 9, 3:35 – 3:50 p.m., ET, in Salon A-B, East Hall, in the Washington Convention Center. The results come from a study in which researchers used advanced amplification technology to search for abnormal DNA circulating in blood samples from patients in a clinical trial of a new therapy for gastrointestinal stromal tumor (GIST). GIST is a mutation-driven cancer of the digestive system that arises in approximately 5,000 people in the United States each year. The technique is particularly valuable, the investigators said, because it can comprehensively detect many different cancer-related mutations from multiple tumors within a single patient, whereas conventional biopsies are able to provide information only on small bits of tumors which are sampled. At a time when therapies are increasingly targeted at specific cancer-causing mutations and where resistance to such therapies is known to be caused by other mutations, it is important for doctors to know the full slate of mutations in all the cancer cells within a patient. Because different GIST cells within a single patient can have different sets of mutations, biopsies of one or two tumors often uncover only a portion of the mutational landscape.

Personalized Immunotherapy Shows Significant Promise for Ovarian Cancer

As many as three quarters of advanced ovarian cancer patients appeared to respond to a new two-step immunotherapy approach -- including one patient who achieved complete remission -- according to research from the Perelman School of Medicine at the University of Pennsylvania that was presented April 6, 2013 in a press conference at the American Academy of Cancer Research (AACR) Annual Meeting 2013 (Presentation #LB-335) in Washington, D.C. The immunotherapy has two steps – a personalized dendritic cell vaccination and adoptive T-cell therapy. The scientific team reports that in the study of 31 patients, vaccination therapy alone showed about a 61 percent clinical benefit, and the combination of both therapies showed about a 75 percent benefit. The findings offer new hope for the large number of ovarian cancer patients who relapse following treatment. The first step of the immunotherapy approach is to preserve the patient's tumor cells alive, using sterile techniques at the time of surgery so they can be used to manufacture a personalized vaccine that teaches the patient's own immune system to attack the tumor. Then, the Penn Medicine team isolates immune cells called dendritic cells from patients' blood through a process called apheresis, which is similar to the process used for blood donation. Researchers then prepare each patient's personalized vaccine by exposing her dendritic cells to the tumor tissue that was collected during surgery. Because ovarian cancer symptoms can be non-obvious and easily mistaken for other issues – constipation, weight gain, bloating, or more frequent urination – more than 60 percent of patients are diagnosed only after the disease has spread to their lymph nodes or other distant sites in the body, when treatment is much less likely to produce a cure compared to when the disease is detected early.