Amyotrophic Lateral Sclerosis (ALS) is a rare and deadly neurological disorder affecting voluntary muscle movement. It typically claims victims’ lives about three years after symptoms begin. In the United States,  the condition is more commonly known as Lou Gehrig’s disease, after the Yankees slugger who died of ALS in 1941. About 20,000 people in the U.S. have ALS and one in 100,000 people develop the disease per year.

Despite years of research, relatively little is known about the causes and risk factors of ALS. This week, understanding of the disease moved a step forward with a study published in PNAS that identified several new genetic variants associated with ALS risk.

A team of scientists led by Francois Gros-Louis and Jean-Pierre Julien of Université Laval in Canada analyzed genetic variants in the CHGB gene in more than 700 French and Swedish people with ALS and 750 people without the disease. Although most of the variants found in the CHGB gene were rare, one of the more common variants was markedly more frequent in those with ALS than in those without. The rarer T version of this SNP, rs742710, was associated with about 2.4 times increased odds of ALS, compared to the more prevalent C version. The SNP also seemed to affect age-of-onset: individuals with the T version of rs742710 tended to develop ALS about 10 years earlier than individuals with two copies of the C version.

(23andMe Complete Edition customers can check their data for rs742710 using the Browse Raw Data feature.)

One of the hallmarks of ALS and some other neurodegenerative diseases is the abnormal aggregation of proteins within cells. Many of these aggregations appear in organelles known as the endoplasmic reticulum (ER) and the Golgi network, which are tasked with processing proteins into their mature forms and readying certain ones to be secreted, or released outside the cell.

Gros-Louis and his team focused on the CHGB gene because of its “guilt-by-association” relationship with SOD1, one of the few established genetic factors linked to ALS. Abnormal SOD1 proteins tend to aggregate in motor neurons of people with ALS, and recent reports have found chromogranin B, the protein encoded by CHGB, near these aggregates.

Chromogranin B is typically secreted from cells like a hormone, and so the researchers hypothesized that genetic variants in CHGB associated with increased risk for ALS might impair secretion of chromogranin B. Sure enough, in cells with CHGB containing the T version of rs742710, almost all of the protein remained sequestered inside the ER/Golgi network.  In cells with normal CHGB, only 40% of the chromogranin B protein was found there.

Previous studies in this area have indicated that stress and damage to the ER and Golgi are a defining characteristic of ALS-affected motor neurons. Gros-Louis and his colleagues suggest that further research be done to investigate whether CHGB variants like rs742710 stress the ER-Golgi system and hasten the deterioration of motor neurons.

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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Scientists are narrowing in on two regions of the human genome that could be responsible for ALS (amyotrophic lateral sclerosis), also known as Lou Gehrig’s disease.

ALS is a neurodegenerative disorder that weakens muscles and paralyzes patients within three years of onset, and has no known cure. The available drug treatment delays progression by only three to five months.

Despite several attempts to find genetic variations associated with the sporadic form of the disease (which accounts for 95% of ALS cases), no association has been found.

A team of researchers from Netherlands, Van Es et al., analyzed the genes of nearly 20,000 people of European descent, including 5,000 ALS patients. Their results, published online this week in Nature Genetics, identified several genetic variations on two chromosomes suspected to affect ALS and other neurological functions.

The study revealed that each copy of the C version of rs12608932, a SNP on chromosome 19, is associated with a 1.2 times increased odds of ALS compared to having two copies of A. This SNP is found near UNC13A, a gene that may be involved in the function of motor neurons, which degenerate and die in ALS patients.

Each copy of the T version SNP rs2814707, located on chromosome 9, is associated with a 1.16 times increased odds of ALS compared to having two copies of C. This SNP was found in a region of the genome previously associated with the rare familial (non-sporadic) version of ALS. Researchers also found an association between the disease and a third SNP located very close to rs2814707.

(23andMe customers can check their data for rs12608932 and rs2814707 using the Browse Raw Data feature.)

There is increasing evidence that ALS belongs to a broader spectrum of neurodegenerative disorders, including Parkinson’s disease, so researchers speculate that genetic associations with ALS may also lead to clues about other disorders of the nervous system.

(Note: A previous genetic association listed in 23andMe’s ALS Research Report, which provides information about lower-impact and preliminary research results, was not replicated in this study.)

SNPwatch gives you the latest news about research linking various traits and conditions to individual genetic variations. These studies are exciting because they offer a glimpse into how genetics may affect our bodies and health; but in most cases, more work is needed before this research can provide information of value to individuals. For that reason it is important to remember that like all information we provide, the studies we describe in SNPwatch are for research and educational purposes only. SNPwatch is not intended to be a substitute for professional medical advice; you should always seek the advice of your physician or other appropriate healthcare professional with any questions you may have regarding diagnosis, cure, treatment or prevention of any disease or other medical condition.

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There’s a high likelihood that a disease of some sort affects you or one of your relatives — every family seems to have ripples in its gene pool that define and shape its health dynamics.

Your family might have a propensity for rheumatoid arthritis or a particular type of cancer. Whatever it is, there can be an instant family bond created by that disease — along with a sense of fate.

That feeling moves some families to action. The Heywood brothers started PatientsLikeMe when one of them, Stephen, was diagnosed with Lou Gehrig’s disease in 1998. Nancy Brinker created a huge force in breast cancer research through the Susan G. Komen Foundation, named for her sister who died of that disease. Michael J. Fox, a father of four, started his remarkable foundation after he was diagnosed with Parkinson’s disease at the age of 30.

But not everyone can garner the resources to create their own company or foundation; it’s hard to know where to turn in trying to make a difference. This summer, 23andMe is launching the Research Revolution to empower more people to jumpstart genetic research into the diseases that affect them and the people they love.

This new research model makes it possible for large groups of people to assemble themselves into large-scale genetic studies without having to raise millions of dollars in funding, and then wait years for things to get rolling. Participants also get access to their own genetic information through the 23andMe Personal Genome Service Research Edition, which offers a snapshot of what their data says about more than 100 diseases and traits. We believe that if you volunteer for research, you should be able to see what you’ve contributed to the effort.

The Research Revolution is going to start with the 10 diseases listed at the bottom of this post. There are several ways you can participate:

* Visit the Research Revolution page and vote for the disease you would most like 23andMe to study.
* If you’re already a 23andMe customer, log into your account and complete any of the 23andWe surveys you haven’t taken yet.
* Spread the word — especially to people who are patients or survivors of the 10 diseases we’re featuring.

There’s strength in numbers. The more people who enroll in the Research Revolution, the more likely it is to make new discoveries about the causes and about the treatments of disease.

Long live the revolution!

The 10 Research Revolution diseases are:

ALS
Celiac Disease
Epilepsy
Lymphoma and Leukemia
Migraines
Multiple Sclerosis
Psoriasis
Rheumatoid Arthritis
Severe Food Allergies
Testicular Cancer

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