In the world's largest brain study to date, a team of more than 200 scientists from 100 institutions worldwide collaborated to map the human genes that boost or sabotage the brain's resistance to a variety of mental illnesses and Alzheimer's disease. Published April 15 in the advance online edition of Nature Genetics, the study also uncovers new genes that may explain individual differences in brain size and intelligence.
"We searched for two things in this study," said senior author Paul Thompson, professor of neurology at the David Geffen School of Medicine at UCLA and a member of the UCLA Laboratory of Neuro Imaging. "We hunted for genes that increase your risk for a single disease that your children can inherit. We also looked for factors that cause tissue atrophy and reduce brain size, which is a biological marker for hereditary disorders like schizophrenia, bipolar disorder, depression, Alzheimer's disease and dementia."
Three years ago, Thompson's lab partnered with geneticists Nick Martin and Margaret Wright at the Queensland Institute for Medical Research in Brisbane, Australia; and with geneticist Barbara Franke of Radboud University Nijmegen Medical Centre in the Netherlands. The four investigators recruited brain-imaging labs around the world to pool their brain scans and genomic data, and Project ENIGMA (Enhancing Neuro Imaging Genetics through Meta-Analysis) was born.
"Our individual centers couldn't review enough brain scans to obtain definitive results," said Thompson, who is also a professor of psychiatry at the Semel Institute for Neuroscience and Human Behavior at UCLA. "By sharing our data with Project ENIGMA, we created a sample large enough to reveal clear patterns in genetic variation and show how these changes physically alter the brain."
In the past, neuroscientists screened the genomes of people suffering from a specific brain disease and combed their DNA to uncover a common variant. In this study, Project ENIGMA researchers measured the size of the brain and its memory centers in thousands of MRI images from 21,151 healthy people while simultaneously screening their DNA.
"Earlier studies have uncovered risk genes for common diseases, yet it's not always understood how these genes affect the brain," explained Thompson. "This led our team to screen brain scans worldwide for genes that directly harm or protect the brain."
In poring over the data, Project ENIGMA researchers explored whether any genetic variations correlated to brain size. In particular, the scientists looked for gene variants that deplete brain tissue beyond normal in a healthy person. The sheer scale of the project allowed the team to unearth new genetic variants in people who have bigger brains as well as differences in regions critical to learning and memory.
When the scientists zeroed in on the DNA of people whose images showed smaller brains, they found a consistent relationship between subtle shifts in the genetic code and diminished memory centers. Furthermore, the same genes affected the brain in the same ways in people across diverse populations from Australia, North America and Europe, suggesting new molecular targets for drug development.
"Millions of people carry variations in their DNA that help boost or lower their brains' susceptibility to a vast range of diseases," said Thompson. "Once we identify the gene, we can target it with a drug to reduce the risk of disease. People also can take preventive steps through exercise, diet and mental stimulation to erase the effects of a bad gene."
In an intriguing twist, Project ENIGMA investigators also discovered genes that explain individual differences in intelligence. They found that a variant in a gene called HMGA2 affected brain size as well as a person's intelligence.
DNA is comprised of four bases: A, C, T and G. People whose HMGA2 gene held a letter "C" instead of "T" on that location of the gene possessed larger brains and scored more highly on standardized IQ tests.
"This is a really exciting discovery: that a single letter change leads to a bigger brain," said Thompson. "We found fairly unequivocal proof supporting a genetic link to brain function and intelligence. For the first time, we have watertight evidence of how these genes affect the brain. This supplies us with new leads on how to mediate their impact."
Because disorders like Alzheimer's, autism and schizophrenia disrupt the brain's circuitry, Project ENIGMA will next search for genes that influence how the brain is wired. Thompson and his colleagues will use diffusion imaging, a new type of brain scan that maps the communication pathways between cells in the living brain.
Project ENIGMA received funding from hundreds of federal and private agencies around the world. Thompson's UCLA coauthors included first author Jason Stein, Derrek Hibar, Rudy Senstad, Neda Jahanshad, Arthur Toga, Rita Cantor, Dr. Nelson Freimer, Roel Ophoff, Kristy Hwang, Dr. Liana Apostolova and Dr. Giovanni Coppola.
The UCLA Department of Neurology encompasses more than a dozen research, clinical and teaching programs. These programs cover brain mapping and neuroimaging, movement disorders, Alzheimer's disease, multiple sclerosis, neurogenetics, nerve and muscle disorders, epilepsy, neuro-oncology, neurotology, neuropsychology, headaches and migraines, neurorehabilitation and neurovascular disorders. The department ranks No. 1 among its peers nationwide in National Institutes of Health funding.
Elaine Schmidt | EurekAlert!
Cryo-electron microscopy achieves unprecedented resolution using new computational methods
24.03.2017 | DOE/Lawrence Berkeley National Laboratory
How cheetahs stay fit and healthy
24.03.2017 | Forschungsverbund Berlin e.V.
Astronomers from Bonn and Tautenburg in Thuringia (Germany) used the 100-m radio telescope at Effelsberg to observe several galaxy clusters. At the edges of these large accumulations of dark matter, stellar systems (galaxies), hot gas, and charged particles, they found magnetic fields that are exceptionally ordered over distances of many million light years. This makes them the most extended magnetic fields in the universe known so far.
The results will be published on March 22 in the journal „Astronomy & Astrophysics“.
Galaxy clusters are the largest gravitationally bound structures in the universe. With a typical extent of about 10 million light years, i.e. 100 times the...
Researchers at the Goethe University Frankfurt, together with partners from the University of Tübingen in Germany and Queen Mary University as well as Francis Crick Institute from London (UK) have developed a novel technology to decipher the secret ubiquitin code.
Ubiquitin is a small protein that can be linked to other cellular proteins, thereby controlling and modulating their functions. The attachment occurs in many...
In the eternal search for next generation high-efficiency solar cells and LEDs, scientists at Los Alamos National Laboratory and their partners are creating...
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are less stable. Now researchers at the Technical University of Munich (TUM) have, for the first time ever, produced a composite material combining silicon nanosheets and a polymer that is both UV-resistant and easy to process. This brings the scientists a significant step closer to industrial applications like flexible displays and photosensors.
Silicon nanosheets are thin, two-dimensional layers with exceptional optoelectronic properties very similar to those of graphene. Albeit, the nanosheets are...
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to simulate these confined natural conditions in artificial vesicles for the first time. As reported in the academic journal Small, the results are offering better insight into the development of nanoreactors and artificial organelles.
Enzymes behave differently in a test tube compared with the molecular scrum of a living cell. Chemists from the University of Basel have now been able to...
20.03.2017 | Event News
14.03.2017 | Event News
07.03.2017 | Event News
24.03.2017 | Materials Sciences
24.03.2017 | Physics and Astronomy
24.03.2017 | Physics and Astronomy