Inflammatory bowel disease (IBD) is a chronic autoimmune disorder – encompassing both Crohn’s disease and ulcerative colitis – that affects more than a million people in the United States. Normally, our immune system works to fight off harmful pathogens that might pass through our digestive tract. In IBD, however, the immune system stays in overdrive and attacks normal intestinal cells. The resulting chronic inflammation causes abdominal cramps, diarrhea, pain and fever, and weight loss.

Most studies of IBD have investigated genetic factors for Crohn’s disease, but a set of articles published this week in Nature Genetics on IBD address two less-explored angles. Two of the studies identify new genetic associations with ulcerative colitis in European and Asian populations. The third study focuses on early-onset IBD (diagnosed prior to age 19), which is typically more severe than adult-onset IBD and is believed to have a stronger genetic component.

In a joint effort, the UK IBD Genetics Consortium and the Wellcome Trust Case Control Consortium 2 identified three genetic variants associated with ulcerative colitis in a group of 4,682 people with the condition and over 10,000 healthy individuals, all of European ancestry. These variants are located in regions of the genome that had not previously been associated with ulcerative colitis .

Each of the three SNPs – rs886774, rs1728785, and rs6017342 – was associated with slightly increased odds of ulcerative colitis. The researchers highlight a number of proteins encoded by genes near these variants that help maintain the lining of the intestine and regulate cell-cell interactions, including HNF4a, E-cadherin, and laminin, though their exact roles in ulcerative colitis are unclear.

(23andMe Complete Edition customers can see their data for SNPs in this post by using the Browse Raw Data feature.** See table at the end of this post.)

The second study, led by Kouichi Asano and Michiaki Kubo of the RIKEN Center for Genomic Medicine in Japan, looked for genetic variants associated with ulcerative colitis in a group of about 1,380 Japanese individuals with the disease and 3,050 individuals without it. Their two strongest associations were SNPs located near genes involved in immune response.

One of these SNPs, rs9263739, is in a region of the genome that encodes antigen-presenting proteins – important for immune system recognition of “self” vs. foreign substances. Antigen-presenting proteins display bits and pieces of proteins or sugars (antigens) from cells and other microorganisms to immune cells that normally ignore “self” antigens but destroy foreign ones. In autoimmune diseases like IBD, the immune system loses the ability to distinguish between the two types of antigens and mistakenly reacts to the body’s own cells.

The other strongly associated SNP, rs1801274, is located in the FCGR2A gene and causes a change to the encoded protein, which is expressed on the surface of several types of immune cells. Previous studies by other groups have shown that this SNP can play a significant role in the development of other autoimmune disorders. The version of the SNP that increased risk for those other disorders, however, is the opposite version compared to the version associated with increased risk for ulcerative colitis in the current Japanese study.

In the third study, a team led by Marcin Imielinski and Hakon Hakonarson of the Children’s Hospital in Philadelphia identified genetic variants associated with early-onset IBD. Almost 3,500 individuals of European ancestry who had been diagnosed with IBD – either Crohn’s disease or ulcerative colitis – before their nineteenth birthday were compared to close to 12,000 individuals free of IBD.

Imielinski’s team identified three SNPs significantly associated with early-onset Crohn’s disease. For two of the SNPs, rs8049439 and rs2412937, the less common version was associated with slightly increased odds of early-onset Crohn’s disease, while the less common version of rs1250550 was associated with slightly decreased odds. They also observed an association between rs4676410 and early-onset ulcerative colitis.

When they conducted a combined analysis of all early-onset IBD cases (Crohn’s and ulcerative colitis), the researchers found that the three genetic variants associated with early-onset Crohn’s disease were associated with early-onset IBD in general.  The effect sizes were similar to those seen when they looked at just Crohn’s disease.  In addition, they identified another SNP associated with early-onset IBD, rs10500264.

Of the four genetic variants associated generally with early-onset IBD, Imielinski and his colleagues consider rs8049439 to be especially important given its proximity to IL27, a gene involved in the immune system. The researchers showed in a small sample that individuals with early-onset Crohn’s disease express the gene at much lower levels than healthy people. IL27 encodes a protein that suppresses inflammatory immune cells in the intestine, so it is possible that lower expression of IL27 contributes to a hyperactive inflammatory response.

Although the biology of IBD is complex, these three studies contribute to a more comprehensive picture of the genetic factors underlying the condition and suggest potential directions for the development of therapeutics.

“This is an evolving story of discovering what genes tell us about the disease,” said Dr. Baldassano from the Children’s Hospital team in a press release. “Pinpointing how specific genes act on biological pathways provides a basis for ultimately personalizing medicine to an individual’s genetic profile.”

* 23andMe does not currently report on rs1728785, so we instead provide information on a perfect proxy for it, rs1170426.

** 23andMe does not currently report on rs886774 or any of its proxy SNPs.

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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More than a million Americans have Parkinson’s disease, and another 50,000 are diagnosed each year. Scientists know that many of the characteristic symptoms of Parkinson’s — tremors, rigid muscles and movement problems — can be traced back to the loss of dopamine-producing brain cells.  But what researchers don’t fully understand is why these cells are damaged in the first place.

For most cases of Parkinson’s, the brain cell damage is probably the result of  complex interactions between multiple genetic and environmental factors.  Despite years of work, however, hardly any of these factors are known.  But now two research groups have identified several genetic variants associated with the risk of Parkinson’s in Asian and Caucasian populations.  Their results were published online this week in the journal Nature Genetics.

One group, led by Wataru Satake, analyzed the DNA of 2,011 Japanese people with Parkinson’s disease and 18,381 controls.  The other group, made up of U.S. and German researchers (Simón-Sánchez et al.), looked at the genetics of 5,074 Caucasians with Parkinson’s and 8,551 without the disease.

Common variations in and around two genes previously associated with rare familial forms of Parkinson’s disease, SNCA and LRRK2, were associated with the risk for Parkinson’s in the Japanese study.  In the Caucasian study, the association with SNCA was strong, but the evidence for an association between Parkinson’s and common variation near LRRK2 was only suggestive.  Given that the association of mutations in this gene with familial forms of Parkinson’s is so strong, Simón-Sánchez et al. nevertheless think that there truly is a role for SNPs near this gene in non-familial forms of the disease.

(See the table at the end of this post information on all SNPs.)

Satake et al. also found that variations in a region of the genome not previously linked to Parkinson’s disease could affect risk for the disease.  This region of chromosome 1 contains several genes, and it is not yet clear which one might be involved in Parkinson’s.  Satake et al. named the region PARK16.  After comparing their data, the U.S./German group also found a link between Parkinson’s disease and the PARK16 region.

A SNP in the BST1 gene was associated with increased risk for Parkinson’s in the Japanese sample, but did not show any link to the disease in the Caucasian sample.  The risk version of this SNP, however, is found at very low levels in Caucasians.  This may have been why Simón-Sánchez et al. were unable to pick it up in their analysis.

Finally, a SNP in the MAPT gene, which has also been associated with familial forms of Parkinson’s, was associated with disease risk in the Caucasian sample, but not in the Japanese.

Work to find common genetic variations affecting the risk for Parkinson’s will no doubt continue as researchers try to identify all of the puzzle pieces relevant to this devastating disease and how they fit together.

“A further increase in the number and size of cohorts for [genomewide association studies] in [Parkinson's disease] will likely reveal additional common genetic risk loci and these, in turn will improve understanding and, ultimately, treatment of this devastating disorder,” conclude Simón-Sánchez et al.

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.

Although variations in the some of the same genes were found in both the Caucasian and Japanese samples, the same SNPs often do not apply to the different populations. People looking up their own data should use the SNPs listed for the ethnicity they identify most closely with.

*Risk version is more common version of SNP.
**Results did not meet strict cut offs for statistical significance, but researchers suggest the associations are nonetheless real.

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The most common type of arthritis, osteoarthritis, occurs due to accumulated wear and tear – welcome to old age! – or from repetitive movements or injury.  Rheumatoid arthritis, on the other hand, is caused by an autoimmune attack on the lining of the joints, resulting in stiffness, muscle aches, and general fatigue. Approximately two million people in the U.S. suffer from rheumatoid arthritis, and although women are affected more often than men, men tend to have more severe symptoms.

Research has identified a number of genetic factors that contribute to one’s risk of developing rheumatoid arthritis, and new studies continue to reveal more genes that seem to be involved in this complex disease. In a report published this week in Nature Genetics, a team led by Soumya Raychaudhuri and Robert Plenge of Brigham and Women’s Hospital in Boston describe three new genetic associations with rheumatoid arthritis risk.

Using a computational algorithm that incorporates information from the scientific literature, Raychaudhuri and his colleagues identified 22 candidate SNPs that have a large number of connections to previously validated genetic risk factors for rheumatoid arthritis. When they tested these SNPs in a set of almost 8,000 Caucasians with rheumatoid arthritis and 12,000 controls, seven emerged as highly significant associations. After combining this study population with that from a previous study – for a total of more than 11,000 individuals with rheumatoid arthritis and 22,000 without  – three of the variants rose to the top.

All three variants are in genes not previously linked to rheumatoid arthritis. Each copy of a C at rs1980422 and each copy of a G  at rs11586238 increased an individual’s odds of developing the condition by 1.13 times. Similarly, each copy of a C at rs548234 increased the odds of rheumatoid arthritis by 1.11 times.

(23andMe customers can see their data for the SNPs currently covered by 23andMe’s service by using the Browse Raw Data feature. 23andMe currently does not report on rs11586238, but does report on a SNP that acts as a perfect proxy for it, rs12405671. The A version of rs12405671 corresponds to the G version of rs11586238.)

These three SNPs are located near genes involved in the immune response, and, in some cases, near genetic variations that have been associated with other autoimmune disorders, such as Crohn’s disease and type 1 diabetes. Although a detailed, cohesive picture of the causes underlying rheumatoid arthritis remains elusive, each new association discovered by researchers contributes to our understanding of the biological players involved in this autoimmune 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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Cisplatin, a cancer chemotherapy drug first approved by the FDA in 1978, revolutionized the treatment of many types of cancer.  Despite its effectiveness, in many cases doctors are forced to reduce the drug’s dose, or abandon it altogether, due to serious side effects on patients’ hearing.

Between 10-25% of adults and up to 60% of children being treated with cisplatin suffer from severe, permanent hearing loss in both ears. This is particularly damaging in kids, because even mild hearing loss can negatively impact learning and social development.

Researchers have suggested that genetic variants that affect the metabolism of cisplatin might explain why some people are susceptible to drug-induced hearing loss, while other patients receiving similar doses are not.  A new report, published online this week in the journal Nature Genetics, has identified variants in two genes that appear to greatly increase the risk of cisplatin-induced hearing loss.  Although the study is a small one, if replicated these findings could one day help doctors make better decisions about how to prescribe cipslatin.

A team led by Colin Ross from the University of British Columbia analyzed the DNA of 162 children (mostly of European ancestry) treated with cisplatin, focusing their search for genetic variants associated with drug-induced hearing loss on 220 genes known to be involved in the absorption, distribution, metabolism and elimination of medications and their breakdown products.

The variants with the largest effects were found in the TPMT gene.  For example, having one or two Cs at rs1142345 increased the odds of cisplatin-induced hearing loss by 10.51 times, although this result was not statistically significant once the researchers adjusted their data to account for the number of SNPs investigated.

(A larger and statistically significant effect was seen with closely related TPMT SNP, rs12201199, that 23andMe does not currently provide data for.  23andMe customers can use the links in this post to check their data using the Browse Raw Data feature.)

Rs1142345, as well as other variants that reduce the function of the TPMT enzyme, have been associated with adverse reactions to a class of drugs called thiopurines that are used as chemotherapy agents and immune system suppressants.

A second SNP associated with cisplatin-induced hearing was rs9332377 in the COMT gene.  Having one or two Ts at this SNP increased the odds of hearing loss by 5.52 times.  This result was also not statistically significant after adjusting the data.

Other variations in the COMT gene have been associated with a variety of traits, including pain sensitivity, willingness to explore new options, recovery from heart surgery, anxiety, and decreased breast cancer risk in tea drinkers.

None of the SNPs identified in this study were associated with hearing loss in children not treated with cisplatin, suggesting that their effect is specific for drug-induced hearing loss.

“These findings suggest that it may be possible identify individuals at higher risk of cisplatin otoxicity [hearing loss] based on genotype, which would improve counseling and treatment options,” the authors write.

They suggest, for example, that children with the riskier versions of the variants identified in this study could be given lower doses of cisplatin or treated instead with carboplatin, a drug that shows nearly similar cancer cure rates as cisplatin, but has less tendency to cause hearing damage.

The authors acknowledge, however, that their results will need to be replicated in independent populations before any decisions about how to use information about these variants in clinical settings can be made.  Research is also needed to understand what, if any, role these variants play in cisplatin-induced hearing loss in adult cancer patients.

Note: Recent studies by other researchers showed that variations in the megalin gene, the GSTP1 gene and the GSTM1 gene were also associated with the risk of cisplatin-induced hearing loss.  The current report from Ross et al. failed to replicate these associations.

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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New research suggests that your skills behind the wheel may be affected by your genes.

To better understand the effects of a variant in the BDNF gene on motor skills learning, Steven Cramer and colleagues at UC Irvine tested 29 subjects in a driving simulator. Their results, published in the journal Cerebral Cortex, might make you think twice about whom you go on your next road trip with.

Subjects sat in front of a screen with their hands firmly planted at “10 and 2″ on a steering wheel and guided their “car” around a track, attempting to stay centered over a black line. The steering was tuned so that subjects had to begin turning before the screen actually changed.

Over the course of 15 trials, all of the study subjects got better at the driving task. But the seven people who had a T rs6265 improved less than those with two Cs. When subjects returned to the lab four days later for a final lap, everyone had forgotten how to drive the simulator a little bit, but those with a T did worse.

“These people [with a T at rs6265] make more errors from the get-go, and they forget more of what they learned after time away,” Cramer said in a press release.

(23andMe customers can check their data for rs6265 using the Browse Raw Data feature.)

The BDNF protein helps to regulate how nerve cells make new connections and maintain old ones. The T version of rs6265, also known as the Val66Met variant, reduces the amount of BDNF available in the brain and has been linked to impaired learning and memory. Studies have shown that stroke victims with this variant don’t recover as well as those who lack it.

But there may be an upside: the variant seems to have a beneficial effect on cognition in people with Parkinson’s disease, Huntington’s disease, lupus and multiple sclerosis.

“It’s as if nature is trying to determine the best approach,” Cramer said. “If you want to learn a new skill or have had a stroke and need to regenerate brain cells, there’s evidence that having the variant is not good. But if you’ve got a disease that affects cognitive function, there’s evidence it can act in your favor. The variant brings a different balance between flexibility and stability.”

See Wired Science for more.

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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In autoimmune disorders, the immune system — which normally protects us from harmful, foreign substances — goes into overdrive and starts attacking the body’s own cells, causing inflammation and organ damage.

Systemic lupus erythematosus (SLE) is an autoimmune disease characterized by chronic, widespread inflammation that can result in arthritis, fever, skin rashes, muscle aches, seizures and fatigue, among other symptoms. Some symptoms can even be life-threatening. Between one and seven out of every 10,000 people is affected by SLE. The disease affects women nine times more frequently than men, and tends to be more prevalent and severe in people of non-European descent. The exact causes of SLE are unknown and there is currently no cure.

For several decades now, researchers have probed the genetic underpinnings of this mysterious disease. Two studies published this week in Nature Genetics identify new genetic variants associated with SLE in European and Asian populations.

In the first study, a team led by Vesela Gateva and Robert Graham of Genentech identified ten novel genetic variants associated with SLE in a European group consisting of more than 3,000 people with the disease and 10,000 people without SLE. Half of these variants were previously associated with other autoimmune diseases, but this is the first time they have been associated with SLE. In addition, the researchers confirmed nine variants previously linked to SLE in other studies.

(23andMe customers can see their data for the SNPs currently covered by 23andMe’s service by using the Browse Raw Data feature. See table at the end of this post.)

Of the previously reported autoimmune variants, Gateva and colleagues note that the A version of rs641153, a known risk variant for age-related macular degeneration, seems to be protective against SLE, although additional research will be needed to confirm this effect.

One of the SNPs not previously associated with SLE or any other autoimmune disease, rs7708392, is in the gene that encodes TNIP1.  The TNIP1 protein is known to interact with TNFAIP3, a protein that genetic studies have previously linked to rheumatoid arthritis, psoriasis and type 1 diabetes — all autoimmune disorders — suggesting that the TNIP1-TNFAIP3 association may play a general role in autoimmunity.

(23andMe does not currently report data for rs7708392.)

In the second study, Jian-Wen Han and Xue-Jun Zhang’s team from Anhui Medical University in China identified 21 genetic variants associated with SLE in more than 4,000 Chinese individuals with the disease and 8,200 individuals without autoimmune disorders. About half of the associations confirmed previous reports in European populations, and half represented novel findings.

Interestingly, one of the new variants they identified — rs10036748 — is also in the TNIP1 gene. Here, each copy of a T increased odds of SLE by about 1.24 times. Many other SNPs associated with SLE in the Chinese study were located in or near genes involved in immune response.

The TNIP1-TNFAIP3 connection and association of variants known to be linked to other autoimmune diseases add to growing evidence that common genetic factors contribute to autoimmunity. These findings may help pave the way for novel therapeutics for autoimmune disease that exploit this shared genetic basis.

Novel SNPs associated with SLE in Europeans (Gateva et al. study)

Novel SNPs associated with SLE in Asians (Han et al. study)

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Previously in The Spittoon, we discussed two papers that identified genetic variants associated with hemoglobin levels in circulating blood.

But blood consists of much more than hemoglobin, and it is responsible for much more than just transporting oxygen. This week Nature Genetics published the results of two of the largest blood studies to date, which together identified dozens of new variants associated with nine blood-related traits.

In addition to red blood cells, which carry hemoglobin, whole blood contains white blood cells—a crucial part of our immune system—and platelets, which are important for clotting. All of these cellular components are suspended in a protein-rich plasma that makes up most of the volume of blood, and maintains the pressure needed to deliver the blood’s cargo throughout a person’s body.

Like hemoglobin levels, measurements of other blood traits can be informative about health. An abnormally high white blood cell count and platelet volume have both been linked to an increased risk for heart attack. These measurements can also indicate the presence of infectious disease, immunological disorders or cancers.

Nicole Soranzo and her colleagues in the HaemGen consortium measured hemoglobin concentration (Hb), red blood cell count (RBC), red blood cell volume (MCV), platelet count (PLT), platelet volume (MPV), white blood cell count (WBC), the amount of hemoglobin per red blood cell (mean corpuscular hemoglobin content, or MCH), and the amount of hemoglobin relative to the size of the cell (mean corpuscular hemoglobin concentration, or MCHC) in more than 14,000 healthy individuals from Europe. They found sixteen new genetic associations with blood traits from fifteen genomic regions not previously thought to be involved.

Santhi Ganesh and her colleagues in the CHARGE consortium measured Hb, MCV, RBC, MCH, MCHC, and the percent of red blood cells in whole blood (hematocrit, or Hct) in more than 24,000 Caucasian individuals from the U.S. and Europe. Here, they found nine new associated variants from eleven previously unassociated genomic regions.

(23andMe customers can see their data for the SNPs currently covered by 23andMe’s service using the Browse Raw Data feature. See table at the end of this post.)

One of the advantages of these studies is the number of traits that they analyzed.

“Until now, few genome-wide association studies have looked beyond single traits,” Soranzo’s co-author Christian Geiger said in a press release. “But, through a systematic analysis of correlated traits we can begin to discover such shared genetic variants, forming the basis for understanding how these processes interact to influence health and disease.”

Both teams noted several genomic regions that play a broad role in blood-related health. The HBS1L-MYB, TFR2-EPO, TMPRSS6 and HFE regions were all associated with at least three different traits. These regions have also been connected to fetal hemoglobin levels and the iron-overload condition hemochromatosis. Of these newly associated variants, many are close to genes that present promising candidates for further research.

Soranzo’s team went further by investigating whether two of the variants associated with increased platelet volume (PLT) rs11066301 and rs11065987, were also associated with coronary artery disease. They analyzed these SNPs in about 9,500 people with coronary artery disease and 10,500 healthy controls. They found that at both SNPs, each copy of a G increased odds of coronary artery disease by about 1.15 times.

(23andMe customers can see their data for rs11065987 by using the Browse Raw Data feature. 23andMe does not report on rs11066301, but we do report on rs11066320, which correlates perfectly with rs110066301. For rs110066320, the A allele corresponds to increased PLT and higher odds of coronary artery disease.)

When the researchers looked more closely at the region where rs11066301 and rs11065987 are located, they found a block of ten SNPs that tend to be inherited together, and which are all associated with increased PLT and risk of coronary artery disease. They also confirmed previous findings from other researchers of association between celiac disease and type 1 diabetes with SNPs in this block.

Data for chimpanzees and multiple human populations point to a relatively recent event in human evolution where the above-mentioned genetic variants swept across European populations — but not East Asian or African populations. Because the block of SNPs is located in an area of the genome involved in immune response, the authors suggest that these mutations may have given some populations a survival advantage against infection, despite increasing the risk for certain diseases.

SNPs associated with blood-related traits

* In some cases, 23andMe does not cover the original SNP, so a proxy SNP that correlates perfectly with the original in Europeans is reported instead.

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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Doctors routinely order the complete blood count (CBC) for their patients because they can learn a lot about a person’s health by measuring the numbers of different types of blood cells in the circulation, their sizes and the ratios between them.

One component of the CBC is usually a measure of the total amount of hemoglobin, the oxygen carrying protein found in red blood cells.  Low levels of hemoglobin can be a sign of nutritional deficiency, autoimmune disease or bone marrow problems, and may result in fatigue, irregular heartbeat and poor growth in children.  Abnormally high levels of hemoglobin can be caused by heart failure, COPD or kidney cancer and are associated with increased risk of stroke.

New research published online in the journal Nature Genetics this week identifies two SNPs that account for a small amount of the variation in hemoglobin levels seen in the population and may help scientists find new ways to treat blood disorders.

John Chambers and colleagues analyzed the DNA from more than 11,000 Europeans in England and Finland and more than 16,000 Indian Asians living in London.  They found rs855791 and rs198846 both impacted hemoglobin levels.

In both the European and Indian study groups, each A at rs855791 and each G at rs198846 led to an approximately 0.1 gram per deciliter (g/dL) decrease in hemoglobin levels. The normal range for hemoglobin levels in adults is 12 to 18 g/dL.

(23andMe does not currently offer data for rs198846.  Customers can use rs1799945 as a proxy for this SNP.  The C version of rs1799945 corresponds to the lower hemoglobin levels G version of rs198846.)

Approximately 25% of the world’s population has hemoglobin levels low enough to be considered anemic.  The World Health Organization has deemed anemia a severe public health problem in India.  Although nutritional iron deficiencies are a large part of the problem in this and other countries with high levels of anemia, it is interesting to note that the versions of rs855791 and rs198846 that lead to lower hemoglobin levels were found at higher frequencies in the Indian study subjects.

Both SNPs identified in this study are in or near genes involved in regulating the body’s iron levels.

Rs198846 is near the HFE gene.  Mutations in this gene cause hereditary hemochromatosis, a condition that can result in iron overload.  The researchers found, however, that the effect of rs198846 is not related to these mutations.

Rs855791 is located in the TMPRSS6 gene.  Mutations in this gene have been shown to cause a serious form of anemia that does not respond to treatment with oral iron supplements.  Chambers says that learning more about how this gene contributes to hemoglobin levels could lead to new treatments for people suffering from chronic hemoglobin problems.

“The enzyme protein produced by the TMPRSS6 gene is a good target for drug development. Designing a drug that enhances TMPRSS6 activity could augment hemoglobin in people such as cancer and kidney failure patients, who suffer from chronically low levels. A different drug that blocked TMPRSS6 enzyme production might bring down high hemoglobin levels,” he said in a statement.

Several other reports published online this week in Nature Genetics (Benyamin et al., Soranzo et al. and Ganesh et al.) also examined genetic contributions to blood traits.  These will be covered later this week here in the Spittoon.  Benyamin et al. and Ganesh et al. also both found evidence for an association between rs855791 and hemoglobin concentration.

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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Our bones are amazing structures, capable of supporting tremendous force through complex motions. They do this day in and day out, year after year as we sit, stand, walk, run, lift, work, and play. But as the elderly among us know all too well, bones are not invincible and become more fragile as we age. As the natural, continuous cycle of bone turnover slows down and becomes unbalanced, bone is broken down faster than it is replaced — and important bone-strengthening minerals like calcium are lost.

Low bone mineral density (BMD) is one of the hallmarks of osteoporosis (literally “porous bones”), a disease that impacts nearly 45 million people in US and is responsible for more than one million fractures each year. Women develop osteoporosis much more frequently than men, especially after menopause. The burden on the health care system is significant and is expected to double over the next 10-15 years as the population ages.

Although it is natural to lose bone mass as we get older, genetic factors are known to play a large role in determining bone mass and the rate at which bone mineral density decreases. The relationship between genetics and BMD is complex, and association studies have implicated many different genes that may play a role. New research published this week in Nature Genetics continues the search for genetic factors and has identified more than a dozen SNPs associated with BMD in Europeans.

The team of researchers, led by Fernando Rivadeneira and Andre Uitterlinden of the Erasmus Medical Center in The Netherlands, used data from the Genetic Factors for Osteoporosis (GEFOS) Consortium containing lumbar spine BMD and femoral neck BMD measurements for almost 20,000 individuals. About half of the variants they identified replicated previously reported genetic associations with BMD, but the other half were new.

Some of the SNPs were associated with lower BMD while others were associated with higher BMD. For instance, individuals with one or more copies of the C allele at rs1366594 tended to have lower lumbar spine BMD than those without, and individuals with one or more copies of the C allele at rs2566755 tended to have higher lumbar and femoral neck BMD.

(23andMe customers can see their data for the SNPs currently covered by 23andMe’s service using the Browse Raw Data feature. See the table at the end of this post.)

The exact biological processes affected by these variants are still unclear, but increasing evidence points to several signaling pathways known to be important in bone biology.

One of these pathways is mediated by the “Wnt” family of proteins; Wnt signaling is important both for proper differentiation of cells responsible for breaking down bone and for the development of cartilage, required for new bone formation. rs87939, for instance, is near the gene that encodes β-catenin, an important node through which Wnt proteins influence cellular processes such as gene expression (this SNP is not on 23andMe’s platform but correlates perfectly with one that is, rs450615). Wnt proteins can also act through other channels potentially affected by additional SNPs identified by this study.

Another pathway implicated by the growing body of research is estrogen signaling. There is no doubt that the drop in estrogen following menopause in women leads to increased risk for osteoporosis, and hormone replacement therapy can have a protective effect. Not surprisingly, estrogen affects numerous biological processes – including bone maintenance – mainly through its role in gene expression. Variants in ESR1, the major estrogen receptor found in bone, have been associated with BMD and osteoporosis, though results are far from conclusive. Rivadeneira and colleagues confirmed the association of a SNP in ESR1, rs2504063, with lumbar spine BMD. Several other SNPs are also located in or near genes that may influence the regulation of bone development.

Osteoporosis is the most common bone disorder in developed countries. One in two women and one in four men over the age of 50 will experience a bone fracture due to the disease. Diets rich in calcium (especially before your mid-30s) and regular exercise can help combat bone loss. Meanwhile, the search carries on for clues that could lead to greater understanding of bone disease and potential avenues for treatment.

SNPs associated with bone mineral density (BMD):

* In some cases, 23andMe does not cover the original SNP, so a proxy SNP that correlates perfectly with the original in Europeans is reported instead.

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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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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