International team uncovers new genes that shape brain size, intelligence

April 15, 2012

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.
-end-
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.

University of California - Los Angeles Health Sciences

Related DNA Articles from Brightsurf:

A new twist on DNA origami
A team* of scientists from ASU and Shanghai Jiao Tong University (SJTU) led by Hao Yan, ASU's Milton Glick Professor in the School of Molecular Sciences, and director of the ASU Biodesign Institute's Center for Molecular Design and Biomimetics, has just announced the creation of a new type of meta-DNA structures that will open up the fields of optoelectronics (including information storage and encryption) as well as synthetic biology.

Solving a DNA mystery
''A watched pot never boils,'' as the saying goes, but that was not the case for UC Santa Barbara researchers watching a ''pot'' of liquids formed from DNA.

Junk DNA might be really, really useful for biocomputing
When you don't understand how things work, it's not unusual to think of them as just plain old junk.

Designing DNA from scratch: Engineering the functions of micrometer-sized DNA droplets
Scientists at Tokyo Institute of Technology (Tokyo Tech) have constructed ''DNA droplets'' comprising designed DNA nanostructures.

Does DNA in the water tell us how many fish are there?
Researchers have developed a new non-invasive method to count individual fish by measuring the concentration of environmental DNA in the water, which could be applied for quantitative monitoring of aquatic ecosystems.

Zigzag DNA
How the cell organizes DNA into tightly packed chromosomes. Nature publication by Delft University of Technology and EMBL Heidelberg.

Scientists now know what DNA's chaperone looks like
Researchers have discovered the structure of the FACT protein -- a mysterious protein central to the functioning of DNA.

DNA is like everything else: it's not what you have, but how you use it
A new paradigm for reading out genetic information in DNA is described by Dr.

A new spin on DNA
For decades, researchers have chased ways to study biological machines.

From face to DNA: New method aims to improve match between DNA sample and face database
Predicting what someone's face looks like based on a DNA sample remains a hard nut to crack for science.

Read More: DNA News and DNA Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.