A large international study has identified three new gene variants associated with body mass index (BMI) levels in adults. The scientific consortium, numbering approximately 200 researchers, performed a meta-analysis of 46 studies, covering gene data from nearly 109,000 adults, spanning four ethnic groups.
In discovering intriguing links to lipid-related diseases, type 2 diabetes and other disorders, the IBC 50K SNP Array BMI Consortium's study may provide fundamental insights into the biology of adult obesity. Scientists from the Center for Applied Genomics at The Children's Hospital of Philadelphia led the study, using the CardioChip, a gene array containing probes for some 50,000 genetic variants across 2,100 genes relevant to cardiovascular and metabolic functions.
The study appeared online Sept. 21 in Human Molecular Genetics.
"BMI is a widely used measure of obesity, which affects one third of U.S. adults, and approximately half a billion people worldwide," said first author Yiran Guo, Ph.D., of Children's Hospital, who led the meta-analysis. "Previous studies have shown that genetics plays an important role in obesity, and this study expands our knowledge of BMI genetics."
The researchers first analyzed a dataset of approximately 51,000 individuals of European ancestry (EA) to discover initial gene signals, and then performed replication studies in another 27,000 EA subjects, as well as 14,500 additional EA individuals. Further analyses of data from approximately 12,300 African Americans, 2,600 Hispanics and 1,100 East Asians strengthened the team's findings.
The researchers uncovered three novel signals, from the genes TOMM40-APOE-APOC1, SREBF2 and NTRK2) that were significantly associated with BMI in adults. All had previously been linked to other important disorders. The APOE locus is well known to be involved in blood lipid regulation and circulation, and plays an important role in Alzheimer's disease. The SREBF2 gene is in the same family as SREBF1, linked to type 2 diabetes in another CardioChip study. Finally, NTRK2 codes for a receptor of the BDNF protein, which is known to be related to BMI and is associated with the eating disorder anorexia.
Anorexia is a special interest of Guo, who holds a Davis Foundation Postdoctoral Fellowship in Eating Disorders. Guo added that the large dataset from the previous studies allowed the researchers "to enhance our understanding of BMI genetics, as well as the interplay between genetic variants and metabolic disorders such as obesity, type 2 diabetes and lipid-related conditions."
Guo also noted that the team was able to test for conditional associations within genes---independent signals from within the same gene locus. In particular, the researchers discovered that two genes, BDNF and MC4R, each harbor two independent signals for BMI. Both genes were among eight genes previously associated with BMI that the current study was able to replicate, including FTO, SH2B1 and COL4A3BP-HMGCR.
Guo concluded that "while the individual effects of each gene may be small, they may provide fundamental clues to the biology of adult obesity." He added that further studies will investigate gene-gene interactions for the same trait.
The Center for Applied Genomics at The Children's Hospital of Philadelphia was the analysis coordinating site of this study. Three of the Center's scientists were senior investigators of the study: Struan F. A. Grant, Ph.D.; Brendan J. Keating, Ph.D.; and Hakon Hakonarson, M.D., Ph.D. All are on the faculty of the Perelman School of Medicine at the University of Pennsylvania.
The National Heart, Lung and Blood Institute, part of the National Institutes of Health, supported this study.
"Gene-centric meta-analyses of 108,912 individuals confirm known body mass index loci and reveal three novel signals," Human Molecular Genetics, published online in Advance Access, Sept. 21, 2012. doi:10.1093/hmg/dds396
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 516-bed hospital recognition as a leading advocate for children and adolescents. For more information, visit http://www.chop.edu.
Dana Mortensen | EurekAlert!
Further reports about: > Applied and Environmental Microbiology > BMI > CardioChip > Eating Disorder > Genetics > Human Molecular Genetics > Human vaccine > Molecular Target > SREBF2 > body mass > gene variant > genetic variant > health services > metabolic disorder > metabolic function > type 2 diabetes
One step closer to reality
20.04.2018 | Max-Planck-Institut für Entwicklungsbiologie
The dark side of cichlid fish: from cannibal to caregiver
20.04.2018 | Veterinärmedizinische Universität Wien
University of Connecticut researchers have created a biodegradable composite made of silk fibers that can be used to repair broken load-bearing bones without the complications sometimes presented by other materials.
Repairing major load-bearing bones such as those in the leg can be a long and uncomfortable process.
Study published in the journal ACS Applied Materials & Interfaces is the outcome of an international effort that included teams from Dresden and Berlin in Germany, and the US.
Scientists at the Helmholtz-Zentrum Dresden-Rossendorf (HZDR) together with colleagues from the Helmholtz-Zentrum Berlin (HZB) and the University of Virginia...
Novel highly efficient and brilliant gamma-ray source: Based on model calculations, physicists of the Max PIanck Institute for Nuclear Physics in Heidelberg propose a novel method for an efficient high-brilliance gamma-ray source. A giant collimated gamma-ray pulse is generated from the interaction of a dense ultra-relativistic electron beam with a thin solid conductor. Energetic gamma-rays are copiously produced as the electron beam splits into filaments while propagating across the conductor. The resulting gamma-ray energy and flux enable novel experiments in nuclear and fundamental physics.
The typical wavelength of light interacting with an object of the microcosm scales with the size of this object. For atoms, this ranges from visible light to...
Stable joint cartilage can be produced from adult stem cells originating from bone marrow. This is made possible by inducing specific molecular processes occurring during embryonic cartilage formation, as researchers from the University and University Hospital of Basel report in the scientific journal PNAS.
Certain mesenchymal stem/stromal cells from the bone marrow of adults are considered extremely promising for skeletal tissue regeneration. These adult stem...
In the fight against cancer, scientists are developing new drugs to hit tumor cells at so far unused weak points. Such a “sore spot” is the protein complex...
13.04.2018 | Event News
12.04.2018 | Event News
09.04.2018 | Event News
20.04.2018 | Physics and Astronomy
20.04.2018 | Interdisciplinary Research
20.04.2018 | Physics and Astronomy