In a new study, researchers from North Carolina State University, UNC-Chapel Hill and other institutions have taken the first steps toward creating a roadmap that may help scientists narrow down the genetic cause of numerous diseases. Their work also sheds new light on how heredity and environment can affect gene expression.
Pinpointing the genetic causes of common diseases is not easy, as multiple genes may be involved with a disease. Moreover, disease-causing variants in DNA often do not act directly, but by activating nearby genes. To add to the complexity, genetic activation is not like a simple on/off switch on a light, but behaves more like a “dimmer switch” – some people may have a particular gene turned all the way up, while others have it only turned halfway on, completely off, or somewhere in between. And different factors, like DNA or the environment, play a role in the dimmer switch’s setting.
According to Fred Wright, NC State professor of statistics and biological sciences, director of NC State’s Bioinformatics Center and co-first author of the study, “Everyone has the same set of genes. It’s difficult to determine which genes are heritable, or controlled by your DNA, versus those that may be affected by the environment. Teasing out the difference between heredity and environment is key to narrowing the field when you’re looking for a genetic relationship to a particular disease.”
Wright, with co-first author Patrick Sullivan, Distinguished Professor of Genetics and Psychiatry at UNC-Chapel Hill and director of the Center for Psychiatric Genomics, and national and international colleagues, analyzed blood sample data from 2,752 adult twins (both identical and fraternal) from the Netherlands Twin Register and an additional 1,895 participants from the Netherlands Study of Depression and Anxiety. For all 20,000 individual genes, they determined whether those genes were heritable – controlled by the DNA “dimmer switch” – or largely affected by environment.
“Identical twins have identical DNA,” Wright explains, “so if a gene is heritable, its expression will be more similar in identical twins than in fraternal twins. This process allowed us to create a database of heritable genes, which we could then compare with genes that have been implicated in disease risk. We saw that heritable genes are more likely to be associated with disease – something that can help other researchers determine which genes to focus on in future studies.”
The study appears online April 13 in Nature Genetics.
“This is by far the largest twin study of gene expression ever published, enabling us to make a roadmap of genes versus environment,” Sullivan says, adding that the study measured relationships with disease more precisely than had been previously possible, and uncovered important connections to recent human evolution and genetic influence in disease.
The Netherlands Twin Register has followed twin pairs for over 25 years and in collaboration with the longitudinal Netherlands Study of Depression and Anxiety established a resource for genetic and expression studies. Professor Dorret Boomsma, who started the twin register, says, “in addition to the fundamental insights into genetic regulation and disease, the results provide valuable information on causal pathways. The study shows that the twin design remains a key tool for genetic discovery.”
Blood samples from the Netherlands were processed by the NIMH Center for Collaborative Genomics Research on Mental Disorders at Rutgers University. NC State research scholar Yi-Hui Zhou and associate professor of statistics Jung-Ying Tzeng contributed to the work. Funding for the study included grants from the National Institute of Mental Health and other NIH Institutes, the Gillings Innovation Lab, the Netherlands Organization for Scientific Research, the Center for Medical Systems Biology, Biobanking and Biomolecular Resources Research Infrastructure, and the European Science Foundation and European Research Council.
Note to editors: Abstract of the paper follows.
“Heritability and genomics of gene expression in peripheral blood”
Authors: Fred A.Wright, NC State University; Patrick F. Sullivan, UNC-Chapel Hill, et al
Published: Online April 13, 2014 in Nature Genetics
Abstract: We assessed gene expression profiles in 2,752 twins, using a classic twin design to quantify expression heritability and quantitative trait loci (eQTLs) in peripheral blood. The most highly heritable genes (~777) were grouped into distinct expression clusters, enriched in gene-poor regions, associated with specific gene function or ontology classes, and strongly associated with disease designation. The design enabled a comparison of twin-based heritability to estimates based on dizygotic identity-by-descent sharing and distant genetic relatedness. Consideration of sampling variation suggests that previous heritability estimates have been upwardly biased. Genotyping of 2,494 twins enabled powerful identification of eQTLs, which we further examined in a replication set of 1,895 unrelated subjects. A large number of local eQTLs (6,988) met replication criteria, whereas a relatively small number of distant eQTLs (165) met quality control and replication standards. Our results provide a new resource toward understanding the genetic control of transcription.
Tracey Peake | newswise
Lethal combination: Drug cocktail turns off the juice to cancer cells
12.12.2018 | Universität Basel
Smelling the forest – not the trees
12.12.2018 | Universität Konstanz
A widely used diabetes medication combined with an antihypertensive drug specifically inhibits tumor growth – this was discovered by researchers from the University of Basel’s Biozentrum two years ago. In a follow-up study, recently published in “Cell Reports”, the scientists report that this drug cocktail induces cancer cell death by switching off their energy supply.
The widely used anti-diabetes drug metformin not only reduces blood sugar but also has an anti-cancer effect. However, the metformin dose commonly used in the...
A research team from the University of Zurich has developed a new drone that can retract its propeller arms in flight and make itself small to fit through narrow gaps and holes. This is particularly useful when searching for victims of natural disasters.
Inspecting a damaged building after an earthquake or during a fire is exactly the kind of job that human rescuers would like drones to do for them. A flying...
Over the last decade, there has been much excitement about the discovery, recognised by the Nobel Prize in Physics only two years ago, that there are two types...
What if a sensor sensing a thing could be part of the thing itself? Rice University engineers believe they have a two-dimensional solution to do just that.
Rice engineers led by materials scientists Pulickel Ajayan and Jun Lou have developed a method to make atom-flat sensors that seamlessly integrate with devices...
Scientists at the University of Stuttgart and the Karlsruhe Institute of Technology (KIT) succeed in important further development on the way to quantum Computers.
Quantum computers one day should be able to solve certain computing problems much faster than a classical computer. One of the most promising approaches is...
12.12.2018 | Event News
10.12.2018 | Event News
06.12.2018 | Event News
12.12.2018 | Health and Medicine
12.12.2018 | Physics and Astronomy
12.12.2018 | Health and Medicine