Forum for Science, Industry and Business

Sponsored by:     3M 
Search our Site:

 

A hidden architecture: Researchers use novel methods to uncover gene mutations for common diseases

26.03.2012
Human geneticists have long debated whether the genetic risk of the most common medical conditions derive from many rare mutations, each conferring a high degree of risk in different people, or common differences throughout the genome that modestly influence risk.

A new study by Brigham and Women's Hospital (BWH) researchers has harnessed data and new analysis tools to address this question in four common diseases: rheumatoid arthritis; celiac disease; coronary artery disease and myocardial infarction (heart attack); and type 2 diabetes.

The study will be electronically published on March 25, 2012 in Nature Genetics.

The researchers developed a new statistical method built upon "polygenic risk score analysis" to estimate the heritable component of these diseases that is explained by common differences throughout the genome.

Their method takes advantage of data from previously published genome-wide association studies, or GWAS, an approach used to scan DNA samples for common genetic markers seen throughout the population—called SNPs (single nucleotide polymorphisms).

According to senior author Robert Plenge, MD, PhD, BWH director of Genetics and Genomics in the Division of Rheumatology, Immunology and Allergy, "We used GWAS data and a Bayesian statistical framework to demonstrate that a substantial amount of risk to these four common diseases is due to hundreds of loci that harbor common causal variants with small effect, as well as a smaller number of loci that harbor rare causal variants."

Using data on rheumatoid arthritis, they estimated that variation in hundreds of locations throughout the genome might explain 20 percent of rheumatoid arthritis risk, after excluding all of the known rheumatoid arthritis genetic risk factors.

They used computer simulations to demonstrate that the underlying genetic risk in rheumatoid arthritis is largely explained by many common alleles rather than rare mutations.

They observed similar results for celiac disease (43 percent), myocardial infarction (48 percent) and type 2 diabetes (49 percent).

"What is remarkable is that our statistical model was broadly applicable to several common diseases, not just rheumatoid arthritis," said Plenge, who is also an assistant professor at Harvard Medical School and an associate member of the Broad Institute of MIT and Harvard. "Our study provides a clear strategy for discovering additional risk alleles for these and likely many other common diseases."

According to the researchers, these methods can be applied to other genome-wide datasets (e.g., GWAS or whole genome sequencing) to estimate the degree to which there is a genetic component.

One exciting possibility is assessing the genetic basis of individual response to drugs.

"Our method may be particularly useful for diseases and related traits that cannot be easily studied in families," said Eli Stahl, PhD, lead study author, BWH research associate and member of the National Institutes of Health-funded Pharmacogenomic Research Network (PGRN). "For traits such as treatment efficacy or toxicity, we often assume there is a genetic basis to the clinical variability observed among patients. Now, we have the statistical tools to quantify the extent to which this is the case directly."

"Our study reinforces a common thread in the literature, that many subtle differences throughout the genome explain much of the differences in risk for individuals for all kinds of diseases—this has powerful implications for the genetic architecture of disease, for risk prediction and prognosis, as well as for basic biology and developing new drug targets," said co-senior author Soumya Raychaudhuri, MD, PhD, BWH Division of Immunology, Allergy and Rheumatology, assistant professor of medicine at Harvard Medical School.

This research was done in collaboration with colleagues from the University of California, Los Angeles; University Medical Center and University of Groningen, The Netherlands; Massachusetts General Hospital; The University of Pennsylvania; Karolinska Institutet at Karolinska University Hospital Solna, Stockholm, Sweden; The Feinstein Institute for Medical Research; University of Toronto, Mount Sinai Hospital and University Health Network; University of Manchester; and University Medical Center, Utrecht.

This research was supported by the National Institutes of Health; the Intramural Research Program of the National Institute of Arthritis, Musculoskeletal and Skin Diseases (NIAMS); the Pharmacogenomics Research Network (PGRN) and National Institute of General Medical Sciences (NIGMS); the Canadian Institutes for Health Research; Ontario Research Fund; and a Canada Research Chair.

Brigham and Women's Hospital (BWH) is a 793-bed nonprofit teaching affiliate of Harvard Medical School and a founding member of Partners HealthCare, an integrated health care delivery network. BWH is the home of the Carl J. and Ruth Shapiro Cardiovascular Center, the most advanced center of its kind. BWH is committed to excellence in patient care with expertise in virtually every specialty of medicine and surgery. The BWH medical preeminence dates back to 1832, and today that rich history in clinical care is coupled with its national leadership in quality improvement and patient safety initiatives and its dedication to educating and training the next generation of health care professionals. Through investigation and discovery conducted at its Biomedical Research Institute (BRI), www.brighamandwomens.org/research, BWH is an international leader in basic, clinical and translational research on human diseases, involving more than 900 physician-investigators and renowned biomedical scientists and faculty supported by more than $537 M in funding. BWH is also home to major landmark epidemiologic population studies, including the Nurses' and Physicians' Health Studies and the Women's Health Initiative. For more information about BWH, please visit www.brighamandwomens.org.

Marjorie Montemayor-Quellenberg | EurekAlert!
Further information:
http://www.brighamandwomens.org

More articles from Life Sciences:

nachricht Researchers develop eco-friendly, 4-in-1 catalyst
25.04.2017 | Brown University

nachricht Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017
25.04.2017 | Laser Zentrum Hannover e.V.

All articles from Life Sciences >>>

The most recent press releases about innovation >>>

Die letzten 5 Focus-News des innovations-reports im Überblick:

Im Focus: Making lightweight construction suitable for series production

More and more automobile companies are focusing on body parts made of carbon fiber reinforced plastics (CFRP). However, manufacturing and repair costs must be further reduced in order to make CFRP more economical in use. Together with the Volkswagen AG and five other partners in the project HolQueSt 3D, the Laser Zentrum Hannover e.V. (LZH) has developed laser processes for the automatic trimming, drilling and repair of three-dimensional components.

Automated manufacturing processes are the basis for ultimately establishing the series production of CFRP components. In the project HolQueSt 3D, the LZH has...

Im Focus: Wonder material? Novel nanotube structure strengthens thin films for flexible electronics

Reflecting the structure of composites found in nature and the ancient world, researchers at the University of Illinois at Urbana-Champaign have synthesized thin carbon nanotube (CNT) textiles that exhibit both high electrical conductivity and a level of toughness that is about fifty times higher than copper films, currently used in electronics.

"The structural robustness of thin metal films has significant importance for the reliable operation of smart skin and flexible electronics including...

Im Focus: Deep inside Galaxy M87

The nearby, giant radio galaxy M87 hosts a supermassive black hole (BH) and is well-known for its bright jet dominating the spectrum over ten orders of magnitude in frequency. Due to its proximity, jet prominence, and the large black hole mass, M87 is the best laboratory for investigating the formation, acceleration, and collimation of relativistic jets. A research team led by Silke Britzen from the Max Planck Institute for Radio Astronomy in Bonn, Germany, has found strong indication for turbulent processes connecting the accretion disk and the jet of that galaxy providing insights into the longstanding problem of the origin of astrophysical jets.

Supermassive black holes form some of the most enigmatic phenomena in astrophysics. Their enormous energy output is supposed to be generated by the...

Im Focus: A Quantum Low Pass for Photons

Physicists in Garching observe novel quantum effect that limits the number of emitted photons.

The probability to find a certain number of photons inside a laser pulse usually corresponds to a classical distribution of independent events, the so-called...

Im Focus: Microprocessors based on a layer of just three atoms

Microprocessors based on atomically thin materials hold the promise of the evolution of traditional processors as well as new applications in the field of flexible electronics. Now, a TU Wien research team led by Thomas Müller has made a breakthrough in this field as part of an ongoing research project.

Two-dimensional materials, or 2D materials for short, are extremely versatile, although – or often more precisely because – they are made up of just one or a...

All Focus news of the innovation-report >>>

Anzeige

Anzeige

Event News

Expert meeting “Health Business Connect” will connect international medical technology companies

20.04.2017 | Event News

Wenn der Computer das Gehirn austrickst

18.04.2017 | Event News

7th International Conference on Crystalline Silicon Photovoltaics in Freiburg on April 3-5, 2017

03.04.2017 | Event News

 
Latest News

NASA's Fermi catches gamma-ray flashes from tropical storms

25.04.2017 | Physics and Astronomy

Researchers invent process to make sustainable rubber, plastics

25.04.2017 | Materials Sciences

Transfecting cells gently – the LZH presents a GNOME prototype at the Labvolution 2017

25.04.2017 | Life Sciences

VideoLinks
B2B-VideoLinks
More VideoLinks >>>