News
Gene provides link between lower
birth weight and type 2 diabetes
A
large international team of researchers, including scientists from the
VU University, has discovered two gene regions that affect a baby’s
size at birth. The research, published in
Nature
Genetics, is the first robust evidence that a well-known link
between lower birth weight and susceptibility to type
2 diabetes has a genetic component. It is widely believed that
the mother’s nutrition can influence both the growth of her baby and its
later risk of disease. However, this latest research confirms that genes
are also important.
The combined effects of the two identified gene regions are quite
substantial. Nine percent of Europeans inherit two copies
of a genetic variant in each region and are, on average, 113g
lighter at birth than the 24 per cent who inherit one or no copy. This
effect is equivalent to the birth weight reduction caused by a mother
smoking four to five cigarettes per day in pregnancy.
The article can be downloaded from the Nature Genetics website or this
website: Publications > Epub papers (Freathy 2010)
Genetic contribution to variation in cognitive function: an fMRI
study in twins
The important new finding of this
study is that patterns of brain activity carry a person’s genetic fingerprint.
More in particular, precisely which network of brain areas a person recruits for
working memory is, at least in part, under genetic control.
It is by now common wisdom that differences in DNA sequence,
transcription and gene expression cause differences in brain structure and in
human behavior. In studies of functional brain activity scientists tend to
emphasize brain activation patterns that can be observed at the group level,
i.e. they tend to focus on those regions of the brain that show the largest
changes in brain activity across all participants in the study. A focus on
average effects across groups may, however, hinder a true understanding of the
cognitive nature of brain activations as patterns of whole brain activity might
differ in important ways between individuals. To which extent this is the case
and whether such activity patterns are under genetic influences is a much
debated topic. A recent paper in Science addresses these questions in
Dutch twin families.
The study in twins and their brothers used functional
magnetic resonance imaging (fMRI) to investigate the genetic contribution to
brain activity during memory tasks comprising numbers. Brain activity was
assessed in male identical twin pairs, and in their brothers. Identical twins
have identical genotypes (they arise after a single fertilized egg divides and
two individuals with the same genes develop) while they share on average 50% of
their genes with their siblings. All participants did the same memory task
twice. The task required them to to memorize a set of
numbers that consisted of either two or four digits. They then had to verify
whether a single digit was contained in the previously memorized set. While
they were memorizing the numbers they were distracted either by doing simple
arithmetic sums (additions and subtractions) or by categorizing pictures of
fruits, vegetables, kitchen utensils, tools).
The functional imaging data of the brain were processed to
yield colored whole brain activation and “heritability maps”. Activation maps
with different colors represent which parts of the brain are more active than
others. Heritability maps show in which parts of the brain genetic mechanisms
contribute to a lesser or higher extent to individual differences in brain
activity.
Brain activation patterns varied considerably among
participants. Notably, the highly individualized nature of these brain activity
patterns was under substantial genetic control, as was evident from the fact
that identical twin pairs showed higher similarities to their cotwins than twins
and their non-twin brothers or than unrelated participants. These observations
support the notion that certain neurobiological foundations of individuality
have a genetic underpinning.
On a more detailed account, two neural networks involved in
working memory were identified. One network was mainly active in the
organization of language and the other network was mainly active in the
organization of spatial-numerical processes. Individuals who memorize numbers
using language-related networks were less effective under mental arithmetic
distraction than individuals who memorize numbers in a spatial-numerical
network. Identical twins showed a remarkable similarity in their network
organization and this similarity was significantly higher than the similarity
with another (non-twin) brother. Our study suggests that individual preferences
for one or the other processing mode, thereby influencing cognitive performance,
are influenced by genetic mechanisms.
The research project was jointly funded by the Deutsche
Forschungsgemeinschaft (DFG) and the Nederlandse Wetenschappelijk Onderzoek
(NWO). The functional imaging data analyses were carried out in the Central
Imaging Facility of the Medical Faculty, RWTH Aachen University
The
study grew out of an interdisciplinary project between six research
institutions: RWTH Aachen University/Germany (Department of Neurology, Section
Neuropsychology: Klaus Willmes – v. Hinckeldey, Jan Willem Koten), VU University
Amsterdam/Netherlands (Department of Biological Psychology: Dorret Boomsma),
University of Bonn/Germany (Institute of Human Genetics: Peter Propping),
Radboud University Nijmegen/Netherlands (Centre for Cognitive Neuroimaging of
the Donders Institute for Brain, Cognition and Behavior: Peter Hagoort, also
director at the Max-Planck Institute for Psycholinguistics, Nijmegen),
Maastricht University/Netherlands (Department of Cognitive Neuroscience at the
Faculty of Psychology and Neuroscience: Rainer Goebel, also a member of the
Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands
Academy of Arts, Amsterdam), Paris-Lodron University of Salzburg/Austria
(Institute of Psychology: Guilherme Wood).
The article and the Science comment can be found here (Koten 2009). A short clip about this research is available here (bottom of page).
Although it is widely recognized that smoking damages your health, almost 30% of the Dutch population continues to smoke. Previous studies have established that genetic factors contribute to aspects of this behaviour. A large study, which is to be published in the leading American Journal of Human Genetics, has identified a number of interesting groups of genes that play a role in smoking behaviour. The study was led by Jacqueline Vink and Dorret Boomsma of the Department of Biological Psychology at VU University Amsterdam and is a collaborative effort between various national and international research groups.The study used a relatively new method in which the DNA of smokers and non-smokers was tested for more than 500,000 genetic variants. This GWA (Genome Wide Association) study examined whether certain variants were more (or less) present in the genes of smokers than in non-smokers. The researchers focused on the genetic variants located in genes. Genes are pieces of DNA coding for a protein, and proteins play an important role in the body’s biological processes. After having discovered potentially interesting genes, networks were used to visualize their mutual interdependence.
A number of important groups were identified. In one particular group of genes, a common link was detected with glutamate. Glutamate is a neurotransmitter which plays a role in the normal processes of the brain but is more often associated with addiction vulnerability. Genes from this group include GRIN2A, GRIN2B and GRIK2. GRIN2A and GRIK2 were also discovered in a previous study which examined participants’ ability to stop smoking. GRIN2B, though not previously associated with nicotine use in humans, was found in a previous study to have an association with nicotine use in rats. Another important group of genes was formed by the tyrosine kinase genes. The NTRK2 gene belongs to this group and is located in a chromosomal region that has often been identified as an interesting area for addiction vulnerability genes. The GRB14 gene also belongs to this group but is still relatively unknown. The GRB14 protein may well have an inhibitory effect on various tyrosine kinases, which regulate the nicotine acetylcholine receptors and influence the rewarding effect that a person experiences after smoking a cigarette.
By studying gene networks in this way, researchers can gain
a greater understanding of the biological mechanisms involved in addiction
vulnerability. Many different and interactive genes play a role in complex
behavioural patterns associated with smoking. This study is a first step in
mapping the groups of genes.
The results of this study have been published online in the American Journal
of Human Genetics on the 5 March 2009 under the title Genome-wide
association study of smoking initiation and current smoking.
This study is a collaborative work between researchers from:
-VU University Amsterdam; Department of Biological Psychology (Jacqueline
Vink, Eco de Geus, Gonneke Willemsen, Jouke Jan Hottenga and Dorret Boomsma)
and Department of Molecular and Cellular Neurobiology/CNCR (Guus Smit)
-NESDA (Brenda Penninx and colleagues)
-Leiden (Eline Slagboom and colleagues)
-Rotterdam (Cock van Duijn and colleagues)
-GenomEUtwin (colleagues from 5 European countries and Australia)
The article can be found
here.
The website
www.sciencedaily.com recently discussed research conducted with data
from the Netherlands Twin Register and the two resulting publications. The
article can be found
here.
Voluntary exercise does not appear to alleviate anxiety and depression
CHICAGO – Voluntary physical activity does not appear to cause a reduction in anxiety and depression, but exercise and mood may be associated through a common genetic factor, according to a report in the August issue of Archives of General Psychiatry, one of the JAMA/Archives journals.
In the general population, regular exercise is associated with reduced anxious and depressive symptoms, according to background information in the article. Experiments involving specific clinical populations have suggested that exercise causes this reduction in anxiety and depression. However, it is unclear whether this causal effect also occurs in the larger population or whether there is a third underlying factor influencing both physical activity and the risk for mood disorders.
Marleen H. M. De Moor, M.Sc., of VU University Amsterdam, the Netherlands, and colleagues studied 5,952 twins from the Netherlands Twin Register, along with 1,357 additional siblings and 1,249 parents. Participants, all aged 18 to 50, filled out surveys about leisure-time exercise and completed four scales measuring anxious and depressive symptoms.
Associations observed between exercise and anxious and depressive symptoms “were small and were best explained by common genetic factors with opposite effects on exercise behavior and symptoms of anxiety and depression,” the authors note. “In genetically identical twin pairs, the twin who exercised more did not display fewer anxious and depressive symptoms than the co-twin who exercised less.” Exercise behavior in one identical twin predicted anxious and depressive symptoms in the other, meaning that if one twin exercised more, the other tended to have fewer symptoms.
However, the same was not true of dizygotic (fraternal) twins or other siblings, who share only part of their genetic material. In addition, analyses over time showed that individuals who increased their level of exercise did not experience a decrease in anxious and depressive symptoms.
“It is unknown which genes might be involved in voluntary exercise behavior and in the risk for anxiety and depression,” the authors write, but genes involved in the brain pathways that process dopamine, norepinephrine, opioids or serotonin are likely candidates.
The results do not mean that exercise cannot benefit those with anxiety or depression, the authors note, only that additional trials would be needed to justify this type of therapy. “Only voluntary leisure-time exercise is influenced by genetic factors, whereas the other type of exercise [directed and monitored by someone else] is environment-driven. The absence of causal effects of voluntary exercise on symptoms of anxiety and depression does not imply that manipulation of exercise cannot be used to change such symptoms,” they write. “The antidepressant effects of exercise may only occur if the exercise is monitored and part of a therapeutic program.”
Arch Gen Psychiatry. 2008;65[8]:897-905. Available on this website, see 'publications', click 'papers'.
Editor’s Note: This study was supported by grants from the Netherlands Organization for Scientific Research. Please see the article for additional information, including other authors, author contributions and affiliations, financial disclosures, funding and support, etc.
More on this article can be found on these sites:
http://www.medicalnewstoday.com
Subtle differences in DNA of identical twins may help diagnose disease
BIRMINGHAM, Ala. - Identical twins are not completely identical, according to new research from UAB (University of Alabama at Birmingham), jointly with Leiden University Medical Center and VU University, The Netherlands; and Uppsala University and Karolinska Institutet, Sweden. The subtle differences in twin’s DNA may help researchers learn more about a wide range of hereditary diseases and provide a quicker diagnosis for genetic disorders. The findings were published February 14th 2008 in the American Journal of Human Genetics, describing results from an international team led by UAB scientists.
The researchers studied 19 pairs of monozygotic, or identical, twins and found differences in copy number variation in DNA. Copy number variation (CNV) occurs when a set of coding letters in DNA are missing, or when extra copies of segments of DNA are produced.
Humans receive one chromosome from their mother and one from their father, providing for two copies of the genome. In some cases, bits of DNA are missing from a chromosome, leaving the offspring with just one copy of that bit of DNA. In other instances, mutations may produce three, four or more copies of a particular bit of DNA. In most cases, variation in the number of copies likely has no impact on health or development. But in others, it may be one factor in the likelihood of developing a disease.
“The presumption has always been that identical twins are identical down to their DNA,” said Carl Bruder, Ph.D. and Jan Dumanski, Ph.D., of UAB’s Department of Genetics and the study’s lead authors. “That’s mostly true, but our findings suggest that there are small, subtle differences due to CNV. Those differences may point the way to better understanding of genetic diseases when we study so-called discordant monozygotic twins….a pair of twins where one twin has a disorder and the other does not.”
Bruder points out that one twin might develop a particular disease…Parkinson’s, for example…while the other does not. Previously, it was thought that environmental factors were the likely culprits, not genetics. Bruder and Dumanski think their findings indicate that CNV may play a critical role and this can be efficiently studied in identical twins.
“More importantly, changes in CNV may tell us if a missing gene, or multiple copies of a gene, are implicated in the onset of disease,” Bruder said. “If twin A develops Parkinson’s and twin B does not, the region of their genome where they show differences is a target for further investigation to discover the basic genetic underpinnings of the disease.”
The UAB lab is one of the few worldwide that can make the full genome BAC (bacterial artificial chromosome) arrays that are used to find the changed DNA regions.
The research was funded by support from UAB, the Swedish Cancer Society, the Swedish Children’s Cancer Foundation, the U.S. Army Research and Material Command, National Institutes of Health, The Netherlands Genomics Initiative and the National Institutes of Health.