Inflammatory bowel disease (IBD), which can appear as either ulcerative colitis or Crohn’s disease, damages the lining of the digestive tract and leads to abdominal cramps, incomplete digestion and nutritional deficiencies.

Previous research on IBD gave researchers reason to suspect that the CD39 gene, which is involved with inflammatory responses and immunity, may play a role in IBD. Researchers at Harvard University, led by Simon Robson, found further evidence for this gene’s involvement when they removed it from a group of mice. Compared to normal animals, the genetically engineered mice were more susceptible to a drug that causes colitis symptoms similar to those experienced by humans. The results were published this week in the Proceedings of the National Academy of Sciences.

With these animal model results in hand, the researchers turned their attention to humans. They searched a database of genetic information for DNA variants that are predicted to affect how much protein is made from the CD39 gene. One SNP in particular, rs10748643, stood out. Not only did the A version of this SNP correlate with lower CD39 protein levels, but it was also associated with risk for Crohn’s disease. The researchers determined that one copy of A increased the odds of Crohn’s disease by 1.14 times, while two copies increased the odds by 1.3 times.

(23andMe customers can see their data for rs7071836, a SNP that is perfectly linked to rs10748643, by using the Browse Raw Data feature. The A version of rs7071836 is equivalent to the riskier A version of rs10748643.)

Although the study focused only on Europeans, the authors believe their results will also be relevant to people of other ethnicities. The A version of rs10748643 that is associated with increased odds for Crohn’s disease in Europeans is also associated with lower levels of CD39 protein in people with African, Chinese and Japanese ancestry. The importance of this SNP may vary among ethnic groups, however, because the prevalence of the A version differs.

The researchers suggest that future studies will help define exactly how CD39 influences IBD and identify other SNPs that may influence risk for the disease.

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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Addiction to alcohol is associated with the brain’s reward system, which reinforces behaviors that feel good — like drinking — by releasing neurotransmitters such as dopamine and endorphins. With prolonged alcohol consumption, a person’s brain can gradually adapt to the point that excessive amounts of drinking are required in order to produce the same pleasure response, and alcoholism results.

That means genetic factors that influence the biochemistry of the reward pathway, as well as environmental factors that encourage alcohol consumption (such as peer pressure and stress) can increase a person’s alcoholism risk.

Researchers have long suspected that a combination of genetic and environmental causes can act together, increasing alcoholism risk more than either acting alone. But so far little evidence has been found for such an effect.

A new paper to be published in the December issue of Alcoholism: Clinical and Experimental Research has found evidence for a synergistic effect between a genetic variation and level of education in a study of 700 Mexican-Americans. The prevalence of alcoholism among Mexican-Americans is relatively high; Mexican-American men report past heavy drinking at three times the rate of men belonging to other ethnicities.

The researchers, Yanlei Du and Yu-Jui Yvonne Wan of the University of Kansas Medical Center, measured three genetic variants associated with the function of chemicals involved in the brain’s reward system. They also looked at marital status and education level in the study participants.

The study found that of the three genetic variants, two were associated with severe alcoholism (defined by consuming more than 35 drinks per day).

o Having two copies of the A version at the SNP rs1799971, which is located on the opioid receptor gene OPRM1, increased the odds of severe alcoholism 2.16 times.
o Having two copies of a variant in the DRD2 gene, which affects the structure of a receptor for the neurotransmitter dopamine, increased the risk of severe alcoholism 1.85 times.

(23andMe customers can see their data for rs1799971 and rs1799732, which is diagnostic of the DRD2 variant, using the Browse Raw Data feature. For rs1799732, a result of II indicates the riskier variant. SNP rs1799971 has previously been associated with the need for morphine as pain relief after surgery as well as sensitivity to social rejection.)

Of the two environmental factors, only education level had an effect. Those with less than 12 years of education had 1.97 times the odds of severe alcoholism. (Having less than 12 years of education also increased a person’s odds of less-severe alcoholism by about the same amount.)

But when the researchers considered combinations of the three associations, they found that having two A copies of the OPRM1 SNP rs1799971, combined with less than 12 years of education, increased a person’s odds of severe alcoholism 3.3 times.

The researchers suggest that a low education level may magnify the effects of the OPRM1 variant, or that higher education may mask its effects by improving brain function.

However, other factors might be responsible for the effect. For example, it is possible that those who attain an education past high school have other characteristics that make them less likely to become addicted to a substance.

There is no way yet to measure an individual’s vulnerability to alcohol addiction, and the complex interaction between genetics, education and other environmental factors must be further studied to clarify the causes of alcoholism in this and other ethnicities.

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New research suggests the primary genetic mutation that causes alpha-1 antritrypsin deficiency, a condition that results in liver damage and a wide variety of other problems, also affects risk for liver disorders associated with cystic fibrosis.

Cystic fibrosis is an inherited, childhood-onset disorder that causes the lungs, intestines and pancreas to become clogged with mucus, resulting in breathing and digestive problems. Between three and five percent of CF patients also experience liver disease, which leads to scarring that can block blood flow through the organ and increase blood pressure in surrounding vessels.

Liver transplants have been necessary in many of these cases, but the new genetic research may be able to help prevent them by enabling prediction and prevention of CF-associated liver disease.

A team of researchers at the University of North Carolina at Chapel Hill, led by Michael Knowles, analyzed genetic variants in five genes that have been proposed to be involved in cystic fibrosis-related liver disease. The study involved nearly 1,000 patients, both with and without liver symptoms.

The results, published last week in the Journal of the American Medical Association, identified one genetic variation that increases a cystic fibrosis patient’s risk of developing liver disease. Researchers found that each T at the SNP rs28929474 increases odds of liver disease in CF patients by 4.17 times. A T at both copies of this SNP causes alpha-1 antitrypsin deficiency.

Researchers are still searching for genetic variations associated with other complications of cystic fibrosis, including lung disease, intestinal obstruction and diabetes. Further studies on severe liver disease related to cystic fibrosis may reveal more risk factors for severe symptoms that can be detected early in life.

(23andMe customers can check their data for one of the most common CFTR mutations, Delta F508, in the Carrier Status Clinical Report for cystic fibrosis. Data for rs28929474 is available in the Browse Raw Data feature or in the Alpha-1-Antitrypsin Deficiency Carrier Status Report.)

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Prostate cancer, the most common cancer to affect men, kills 30,000 men of all ethnicities each year. The disease is known to have a strong genetic component, and several common DNA variations have been found to affect a man’s risk of prostate cancer. However, previous research has analyzed men of only European and African ancestry, leaving the effects of these genetic variants in Asian men undetermined.

Recently, researchers analyzed Japanese men for several genetic variants previously linked to prostate cancer in European and African American populations. The study found that some of these variants also affect the risk of developing prostate cancer in Asian men.

A team from Boston and Japan led by Matthew Freedman searched for risk variants by scanning the genomes of nearly 1,350 Japanese men, including more than 300 prostate cancer patients. The results, published online last week in the Journal of the National Cancer Institute, provide evidence that five out of 23 SNPs previously associated with prostate cancer among Europeans and African Americans also impact risk in this Asian population.

(23andMe customers can use the links in the table at the end of this post to see their data for the five SNPs using the Browse Raw Data feature. Note: Even though only men can develop prostate cancer, women may pass on the risk versions of these SNPs to their sons, possibly increasing their risk.)

Although not every one of the five SNPs had a statistically significant association on its own, the group of SNPs had an association with prostate cancer. Men who carry six or more of the 10 possible risk copies at any of the five associated SNPs (people have two copies of each SNP) had 6.22 times increased odds of developing prostate cancer than men with two or fewer risk copies. The SNPs were not linked to the progression of prostate cancer, but SNPs rs6983561 and rs4430796 were associated with a younger age at diagnosis.

Further research with a larger number of patients will be needed to determine how several of these SNPs may have differing effects between populations of different ancestry, suggests John Ioannidis in an accompanying editorial published in the Journal of the National Cancer Institute.

“When each SNP is analyzed separately, there are clear signs of divergent risks in Asian versus European populations,” Ioannidis wrote. Several other SNPs may also have considerably different effects in these and African American populations, so more research is needed to accurately determine an individual’s risk for prostate cancer.

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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We may be another step closer to discovering what makes us human.

A new study published online this week in Genome Research has pinpointed three genes in humans that may genetically differentiate us from chimps and other primates. Genetically we are very similar to chimps, so most of the differences researchers have observed to date regard physical appearance and behaviors.

The new study found several genes that were once silent and nonfunctional in our primate ancestors, and seem to have awakened around the time that humans formed a new evolutionary branch.

Researchers at the University of Dublin compared sections of the human genome with those of chimps and other primates to find active genes that are absent from the chimp genome. They found three human genes, CLLU1, C22orf45 and DNAHI0OS, that were present but inactive in non-human primates.

At the location of each of the three human genes, a disabling sequence of DNA was found in the genomes of the chimp, macaque, gorilla, gibbon and partially in the orangutan. The study suggests that the awakened human genes not only shed their disabling components, but gained “enabling” sequences that helped them do the work of forming proteins in the body.

Previous research found that genes arising from inactive DNA were present in flies and yeast. The study suggests there may be a total of 18 awakened genes in humans, but researchers were limited to analyzing only a part of the 24,000-gene human genome.

The functions of these novel genes are not yet known, but it is tempting to infer that these genes, specific to humans, are responsible for the attributes that differentiate us from other primates.

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New genetic research may explain why Fluffy is so fluffy.

A study led by researchers at the National Human Genome Research Institute scanned 1,000 dogs from 80 breeds, looking for genes associated with different hair types: curly, wavy, straight, wiry, long and any combination of these. Their results, published online last week in Science, show that variations in just three genes account for nearly all of the different types of coats worn by man’s best friend.

The study found that purebred dogs with similar hair types were found to have similar variations at three particular genes, RSPO2, FGF5 and KRT71.

A particular variation in the RSPO2 gene was linked to wiry hair in a pattern that gives dogs a moustache and eyebrows, such as in a schnauzer.

A variation in the FGF5 gene was associated with long hair, whether silky or fluffy, like that in a Pomeranian. Variations in the KRT71 gene seem to affect the extent of hair curl in dogs like Irish water spaniels.

The FGF5 and KRT71 genes have been shown in previous studies to also affect hair type in cats and mice, suggesting that their effects may be relevant to all mammals, including humans.

Some dogs have all three of the variations identified by the researchers, including Portuguese water dogs, a breed you may have seen taking walks on the White House lawn.

Short-haired dogs like beagles, who don’t exhibit any of the different types of hair studied by the researchers, all seem to have the ancestral versions of the FGF5, RSPO2 and KRT71 genes. The study also found that wolves carry the non-mutated forms of these genes, suggesting that the different types of hair evolved after the evolutionary split between the two canine subspecies.

Despite what we know about the genetics of hair type in dogs, there is little known about what makes human hair straight, wavy, curly, frizzy, kinky, woolly or helical. While hair type in dogs is easily classified, studying human hair is not as simple. Some scientists have suggested characterizing hair by curl ratios and other measurements, but our diverse biological background poses a challenge in classifying human hair types for research.

This study could help researchers better understand the genetics of hair type in humans. It has also unleashed new possibilities for human disease research because these three genes that affect dogs’ coats also regulate many other processes in living organisms, giving researchers a chance to study how powerful genes interact with each other.

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A new genetic screening process has helped researchers understand the genetic causes of cancer, such as how mutations accumulated in a person’s life can cause leukemia.

The study shows that by comparing a person’s own DNA to that of their cancerous cells, researchers can find DNA mutations that may have led to abnormal cell growth, or cancer.

After sequencing a single leukemia patient’s healthy and cancerous DNA, researchers at Washington University School of Medicine in St. Louis were able to pinpoint several mutations out of hundreds that appeared likely to have contributed to his cancer’s development. He is the second patient with acute myeloid leukemia (AML) to have his entire genome and that of his cancerous tissue fully sequenced, rather than just the portions that are known to be prone to cancer-causing mutations.

“If we only look at genes with known or suspected links to cancer, we’ll miss many mutations that are potentially relevant,” co-author Richard Wilson said in statement.

The study by Mardis et al., published in The New England Journal of Medicine, identified a total of 750 mutations in the patient’s AML genome. Most of them proved irrelevant, but 64 were likely to be cancer-related. Two previously known mutations were newly linked to leukemia.

Timothy Lay, senior author of the study, explained in a statement that most patients with this type of leukemia are treated similarly, at least in the beginning. This study’s patient, for example, received various chemotherapy drugs. Defining cancer mutations could help determine which patients need aggressive treatment, such as a stem cell transplant, and which could be effectively treated with less intense therapies.

Personalized sequencing of entire cancer genomes is possible now because the accuracy and cost of genome sequencing technology has dramatically improved. This study took only a few months at one-third the cost of the first AML patient, who was sequenced only one year ago.

To date 350 cancer mutations are known, but thousands of cancer genomes will need to be screened to truly explain the genetic basis for cancer. This information could be used not just to guide physicians to the most effective treatment, but also to inform patients about their prognosis.

But do patients even want to know?

A recent study published in the Journal of Genetic Counseling suggests they do. Researchers found that 98 of 99 patients with ocular melanoma, a rare, untreatable eye cancer, said they wanted to know if their cancer had a genetic marker that gave them a 50 percent chance of dying within five years. Patients were relieved when the risk was low, but even when the risk was high they were enabled to plan financially and make the most of their time alive.

This very personalized medicine will continue to be driven by improved diagnostic testing, finding more predictive disease markers, and new therapies directed at cancer-specific mutations, James Downing wrote in a recent editorial published this month in The New England Journal of Medicine. He believes this technology will likely be used clinically long before we have a complete knowledge of cancer genes.

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AIDS used to be considered a male-specific health problem — but now, the majority of its victims are female.

Those numbers aside, some studies have shown that certain females take much longer than males to progress to AIDS after being infected with HIV. Now, researchers have now found a mechanism that might explain this difference.

A two-stage study by Siddiqui et al. identified a genetic variant on the X chromosome that may slow progression from HIV-1 to AIDS in women. The study analyzed both primates and humans, demonstrating that genetic association findings can successfully translate across species, even over an evolutionary distance of 25 million years.

The researchers first analyzed 136 rhesus monkeys infected with SIV (simian immunodeficiency virus). They found a common genetic marker on the X chromosome among those monkeys that progressed slowly to AIDS-related disease. Researchers then studied 303 HIV-infected humans and found an analogous marker on the X chromosome —the SNP rs5968255 — that may affect progression to AIDS in human females.

The results, published in the online version of The American Journal of Human Genetics, indicate that in humans, females with one copy of the C version of rs5968255 progressed to AIDS more slowly than either females with TT or males with a C or T. (Note that females have two X chromosomes, while males only have one.)

Females with one copy of the C version of the SNP took an average of eight years to progress from HIV infection to AIDS, nearly four times less than females with no copies or males. Women with two copies of C are so rare that none were found in the study.

Previous research has linked some degree of HIV resistance to a mutation in SNP i3003626, which is in a gene that encodes the CCR5 receptor.

(23andMe customers can check their data for rs5968255 using the Browse Raw Data feature. Information on i3003626 is available in the Resistance to HIV/AIDS Clinical Report.)

The CT genotype of rs5968255 is more frequent among Asians than Europeans or Africans, suggesting that future research may find that HIV-1 positive Asian females have a slower progression to AIDS. Future studies may also be able to use this X chromosomal variant as a clue toward new drug development for both genders.

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The Rexes and Spots of the world have been man’s best friend for 15,000 years. But when and where did humans begin domesticating these furry companions?

Previous theories suggested that the domesticated dog originated in East Asia and then spread to Africa, Oceania and the Americas. But a recent study by Cornell University researchers has found Mr. Chompers may not have originated in East Asia after all.

Boyko et al. analyzed more than 300 SNPs throughout the genome, as well as a chunk of the maternally inherited mitochondrial DNA and an assortment of other genetic markers in hundreds of village dogs from seven different regions of Egypt, Uganda and Namibia, along with African dog breeds, Puerto Rican street dogs, and mixed-breeds from the United States.

The results, published online ahead of print this month in the Proceedings of the National Academy of Sciences, showed that African village dogs were the most genetically diverse of all the dogs screened. This diversity was comparable to that in East Asian village dog populations.

Mixed-breed dogs and even African breeds, such as Pharaoh hounds and Salukis, lack such genetic diversity since they have been artificially selected and bred.

African village dogs consistently showed this diverse, indigenous ancestry, with the exception of dogs from central Namibia and Giza who showed genetic signs of some mixing with other non-native dogs. This mixing could be due to earlier mating with human-bred dogs or the relative proximity of Giza to Eurasia, which is home to most known breeds.

“Like ancient human populations, these ancient dog populations developed genetic signatures characteristic of their geographic locale,” the authors wrote.

Africa has the highest amount of genetic diversity in humans because humans originated and have been living there longer than on any other continent. Similarly, the high genetic diversity of African village dogs suggests that our canine friends may have also originated in Africa. But the similar level of diversity among East Asian village dogs means that region can’t be ruled out as the birthplace of Canis lupus familiaris. So, more research will be needed to determine exactly when and where canines diverted from baring fangs to chasing boomerangs.

Photo credit: Corin Boyko

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