Will the Wellcome Trust and the Consortium Find that MS and Type 1 Look the Same Genetically Too? Paternal Age is High and These Disorders Increase

Do these variants come into the population with advancing paternal age? Is that why type 1 is almost 90% de novo/non-familial and rising 3% every year with high paternal age? Why is MS going to look like type 1 too?





High Average Paternal Age is Why Type 1 Diabetes, MS, Probably Crohn's, AutoImmune Thyroid Disorders INCREASE There Is A Male Biological Clock and Advancing Paternal Age Equals Genetic Disorders!



Source: Wellcome Trust
Date: June 7, 2007
More on: Diseases and Conditions, Diabetes, Chronic Illness, Stroke Prevention, Genes, Heart Disease

Largest Ever Study Of Genetics Of Common Diseases Published


"The link between type 1 diabetes and Crohn's disease is one of the most exciting findings to come out of the Consortium," says Professor John Todd from the University of Cambridge, who led the study into type 1 diabetes. "It is a promising avenue for us to understand how the two diseases occur. The pathways that lead to Crohn's disease are increasingly well understood and we hope that progress in treating Crohn's disease may give us clues on how to treat type 1 diabetes in the future."

Research from the Consortium has already played a major part in identifying the clearest genetic link yet to obesity and three new genes linked to type 2 diabetes, published in April in advance of the main study. It has found independently a major gene region on chromosome 9 identified by independent studies on coronary heart disease.

Researchers analysed DNA samples taken from people in the UK -- 2,000 patients for each disease and 3,000 control samples -- to identify common genetic variations for seven major diseases. These are bipolar disorder, Crohn's disease, coronary heart disease, hypertension, rheumatoid arthritis and type 1 and type 2 diabetes. For each disease, the researchers will study larger population samples to confirm their results.

Although the human genome is made up of more than three billion sub-units of DNA, called nucleotides (or bases), most of these show little in the way of differences between individuals. A substantial part of the variation in DNA sequence between individuals is due to single-nucleotide polymorphisms (differences), also known as SNPs. There are approximately 8 million common SNPs in European populations. Fortunately, because SNPs that lie close together on chromosomes often tell quite similar stories, researchers in the Consortium were able to explore this variation through analysing a subset of these SNPs (in fact approximately 500,000).

"Human genetics has a chequered history of irreproducible results, but this landmark collaboration of scientists in Britain has shown conclusively that the new approach of analysing a large subset of genetic variants in large samples of patients and healthy individuals works," says Professor Donnelly. "We are now able to effectively scan most of the common variation in the human genome to look for variants associated with diseases. This approach will undoubtedly herald major advances in how we understand and tackle disease in the future."

Further analysis as part of the Consortium will be looking at tuberculosis (TB), breast cancer, autoimmune thyroid disease, multiple sclerosis and ankylosing spondylitis. The results are expected later this year.

Genetic Variants for Type 1 Type 2 Diabetes, Crohn's, Rheumatoid Arthritis,Bipolar, Coronary Heart Disease, Hyperstension Located

From arthritis to diabetes: scientists unlock genetic secrets of diseases afflicting millions


· Huge study covers seven common illnesses
·

Alok Jha, science correspondent
Thursday June 7, 2007
The Guardian

Read the whole article at the Guardian

It's been much more challenging to identify the rather common variants in diseases such as diabetes and Crohn's disease, where there are multiple genes involved but the effects of individual genes has been much smaller," said Mark Walport, director of the Wellcome Trust.

By studying the DNA from 17,000 people, the 50 research groups identified 24 new genetic links for bipolar disorder, Crohn's disease, heart disease, type 1 and type 2 diabetes, rheumatoid arthritis and high blood pressure, tripling the number of genes already associated with them.

"This study is a landmark in the field of diabetes research," said Karen Addington of the Juvenile Diabetes Research Foundation. Dr Walport said that the study, one of the largest genetic research projects to date, had carried out genetic analysis at a "scale that's never been done before."

Research into the links between genes and disease has focused on small numbers of samples, often from relatives who share a higher than usual risk of suffering a particular illness. But the new approach pioneered by the research team, known as a genome-wide association study, heralds the future for this kind of research.

In the study, scientists analysed DNA samples from 2,000 patients per disease, comparing them with 3,000 "control" samples from healthy volunteers and looking at around 500,000 genetic differences in each sample. The full results of the Wellcome trust Case Control Project are published today in Nature and Nature Genetics. "Just a few years ago it would have been thought wildly optimistic that it would be possible in the near future to study a thousand genetic variants in each of a thousand people," said Dr Walport.

Main findings

Crohn's disease: Eight new genetic links were found to increase a person's susceptibility to this illness, which affects between 30,000 and 60,000 people in the UK. Having a single copy of any of the disease variants of these genes increases the risk by up to 40%.

Diabetes: Type 1 diabetes affects around 350,000 people in the UK; 1.9 million people have type 2. The study highlighted four new regions of the genome that increase the risk of type 1 diabetes. The research also confirmed that Type 2 diabetes has a genetic component.

Bipolar disorder: Also known as manic depression. It is marked by extreme mood swings and affects abut 100 million people worldwide. Many of the genes identified in the study seem to play a key role in the way nerve cells in the brain talk to each other.

Coronary heart disease: The study found several genetic regions that increased the risk of heart disease. The risk increased by 50% in people carrying one version of the disease variant. For those carrying both the risk was almost doubled. Coronary disease is Britain's biggest killer, claiming 105,000 lives each year.

Hypertension (high blood pressure): The research suggests that high blood pressure arises because of a wide range of interacting factors, including three genes identified in the study . The disorder affects more than 16 million Britons and a billion people worldwide.

Rheumatoid arthritis: This disease affects almost 400,000 people in the UK. The project identified three locations in the genome that had a possible role in predisposing people to the condition.

neuroendocrine cells of the intestinal epithelium have a role to play in Crohn's Disease

Another neuroendocrine disorder probably due to increased paternal age. I've heard there is an epidemic of children with Crohn's.


Researchers Discover Genes Associated with Crohn’s Disease
Apr 17 2007, 12:38 PM EST
GEN News Highlights


A search of the entire human genome revealed three genes linked to increase the risk of developing inflammatory bowel disease. Additionally, the study identified two regions of the genome where genetic risk factors are located but no known genes were implicated.

The researchers found that PHOX2B, NCF4, and ATG16L1 constitute genetic risk factors for Crohn's disease or colitis as well as numerous biological pathways not previously thought to play a role in Crohn's disease.

"The identification of the PHOX2B gene in this study may implicate a role for neuroendocrine cells of the intestinal epithelium as having a role to play in Crohn's Disease,” reports John D. Rioux, Ph.D., associate professor of medicine at the Montreal Heart Institute and the Universite de Montreal.

“In addition, the identification of the NCF4 gene indicates that altered reactive oxygen species production, important in the generation of an effective antimicrobial response, may lead to increased risk of developing the disease.”

The fact that the authors also found strong association of the ATG16L1 gene provides further evidence that an individual's response to microbes has an influence on susceptibility to Crohn's disease.

In addition to demonstrating its association to the disease, the authors found that ATG16L1 is essential for the normal autophagic process used to degrade worn-out cellular components and help eliminate some pathogenic bacteria. "We propose that genetic variation in the ATG16L1 gene leads to alterations in how the body uses autophagy and therefore may result in increased persistence of both cellular and bacterial components, leading to inappropriate immune activation and increased risk of Crohn's disease" adds Dr. Rioux.

The report appears in the April 15 online edition of Nature Genetics.

Researchers Discover Genes Associated with Crohn’s Disease
Apr 17 2007, 12:38 PM EST
GEN News Highlights


A search of the entire human genome revealed three genes linked to increase the risk of developing nflammatory bowel disease. Additionally, the study identified two regions of the genome where genetic risk factors are located but no known genes were implicated.

The researchers found that PHOX2B, NCF4, and ATG16L1 constitute genetic risk factors for Crohn's disease or colitis as well as numerous biological pathways not previously thought to play a role in Crohn's disease.

"The identification of the PHOX2B gene in this study may implicate a role for neuroendocrine cells of the intestinal epithelium as having a role to play in Crohn's Disease,” reports John D. Rioux, Ph.D., associate professor of medicine at the Montreal Heart Institute and the Universite de Montreal.

“In addition, the identification of the NCF4 gene indicates that altered reactive oxygen species production, important in the generation of an effective antimicrobial response, may lead to increased risk of developing the disease.”

The fact that the authors also found strong association of the ATG16L1 gene provides further evidence that an individual's response to microbes has an influence on susceptibility to Crohn's disease.

In addition to demonstrating its association to the disease, the authors found that ATG16L1 is essential for the normal autophagic process used to degrade worn-out cellular components and help eliminate some pathogenic bacteria. "We propose that genetic variation in the ATG16L1 gene leads to alterations in how the body uses autophagy and therefore may result in increased persistence of both cellular and bacterial components, leading to inappropriate immune activation and increased risk of Crohn's disease" adds Dr. Rioux.

The report appears in the April 15 online edition of Nature Genetics.