The candles on your birthday cake tell you how many years you’ve lived through, but they might not be a reflection of your biological age.

Little bits of DNA called telomeres protect the ends of chromosomes.  Over time, through repeated rounds of cell division, telomeres get shorter and shorter.  Thus, telomere length is a marker of biological aging. Research recently published in the journal Nature Genetics that found a common DNA variation associated with telomere length suggests that some people are genetically programmed to age at a faster rate.

Researchers from the University of Leicester and King’s College London analyzed the DNA of more than 12,000 Europeans.  They found that each copy of the less common G version of SNP rs12696304 was associated with about a 75 base pair reduction in average telomere length.  This is equivalent to about 3.6 years of biological aging as measured by telomere length loss.

(23andMe does not currently provide data for rs12696304.  The SNP rs6793295 can be used as a substitute in European populations.  Each C a person has at rs6793295 is associated with a reduction in telomere length compared to someone with TT at this SNP.  Complete Edition customers can check their data using the Browse Raw Data feature.)

This finding could have important implications because biological aging isn’t just a matter of wrinkles and aching joints.  Shorter telomeres have been linked with age-associated conditions such as heart disease and certain types of cancer.  But that’s not to say that people with variants that predict shorter telomeres should give up on doing all they can to keep young.

“Genetically susceptible people may age even faster when exposed to proven ‘bad’ environments for telomeres like smoking, obesity or lack of exercise—and end up several years biologically older and succumbing to more age-related disease,” said one of the study’s senior authors, Tim Spector of King’s College London, in a press release.

• A previous Spittoon post about telomeres can be found here.
• You may have heard about telomeres in the news recently: The Nobel Prize in Physiology or Medicine 2009 was awarded jointly to Elizabeth Blackburn, Carol Greider and Jack Szostak “for the discovery of how chromosomes are protected by telomeres and the enzyme telomerase.”

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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Cancer of the pancreas, which strikes more than 40,000 men and women in the United States each year, is an especially deadly malignancy.   There is no effective screening test for the disease and it is usually not detected until it has spread throughout the body.  The five-year survival rate is only about 5%.

Understanding more about the genetic factors that impact pancreatic cancer has the potential to improve prevention and early detection methods, and open new avenues for treatment.  In 2009 one of the first genomewide association studies of pancreatic cancer showed that a SNP on chromosome 9 was associated with risk of the disease.  This finding was not only one of the first strides into understanding the role of common variation in the disease, but it also added new evidence to the decades-long association between type O blood and lower risk for pancreatic cancer.

Now researchers from the same group have found variations in three other regions of the genome that also affect pancreatic cancer risk.  The results, based on an analysis of 3,851 cases and 3,934 controls of mainly European ancestry, were published online this week in the journal Nature Genetics.

The first of the newly identified genomic regions, located on chromosome 13, has been shown by other researchers to be frequently deleted in a variety of cancers, including pancreatic cancer.  There is also evidence that there might be a gene in this region that affects breast cancer susceptibility.  In the current study, the strongest link to pancreatic cancer was with SNP rs9543325.  Having one copy of the C version of this variant increased the odds of pancreatic cancer by 1.23 times compared to those with two copies of the more common (in Europeans) T version.  Having two copies of a C increased odds of the disease by 1.61 times.

The second region the researchers linked to pancreatic cancer risk was on chromosome 1.  Of several variants with statistically significant associations, the strongest was rs3790844. The less common G version of this variation decreased risk of the disease.  Having one copy of a G was associated with 0.75 times odds of pancreatic cancer, while having two copies was associated with 0.64 times odds.

All of the chromosome 1 variants identified by the researchers are located in and around a gene called NR5A2, which appears to be critical for embryonic development and has links to cell growth and division.  All of these functions make it a strong candidate for a gene that is involved in cancer.

The final genomic region associated with pancreatic cancer in this new study is on chromosome 5.  One SNP, rs401681, showed a significant association with the disease.  One copy of a T at this variation was associated with 1.20 times increased odds of pancreatic cancer.  Having two copies of a T increased the odds by 1.41 times.

(23andMe Complete Edition customers can use the links above to check their data for the SNPs identified in this study.)

Rs401681 is near two genes, CLPTM1L and TERT, which have both been linked to cancer.  Previous research has shown that the more common C version of this variation is associated with increased risk of basal cell carcinoma (a type of skin cancer), as well as lung, bladder, prostate and cervical cancer.  There is also suggestive evidence that the C version of rs401681 is associated with increased risk of endometrial cancer.  On the other hand, the T version of rs401681 that was shown to be associated with increased risk of pancreatic cancer in this study has also been found to be associated with increased odds of cutaneous melanoma (another type of skin cancer), and possibly colorectal cancer.

Another research finding of note is that a SNP very near to rs401681 may be associated with the levels of DNA damage caused by smoking.  This is of particular interest because smoking is one of the major risk factors for pancreatic cancer.

The authors of the current study say that more research will be needed to assess how the newly identified genetic variants can be combined with known risk factors for pancreatic cancer—smoking, obesity, diabetes and family history—to identify people who are at high risk for the disease.  They also suggest that further research into the three genomic regions they identified will help guide studies investigating the biological mechanisms underpinning pancreatic cancer.

Pancreatic cancer has received increased media attention in the last year or so due to several high profile people being affected by the disease.  Actor Patrick Swayze died of pancreatic cancer in September 2009.  Randy Pausch, Carnegie Mellon professor and author of “The Last Lecture,” lost his battle with the disease in 2008. Supreme Court justice Ruth Bader Ginsberg had an early stage pancreatic tumor removed in 2009.

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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A new study has identified more common genetic variants associated with increased risk for cleft lip and palate.  Combined with two previous studies (more here and here), there are now four variations that have been associated with this birth defect that affects about one out of every 700 children born.

Clefting results from improper fusing during fetal development of the different elements that will make up the lower part of the face.  For some children only the lip is affected, while others have clefting of both the lip and palate.  Cleft palate alone is much more rare.

An international team led by German researchers analyzed the DNA of 399 people born with cleft lip with or without cleft palate and 1,318 controls.  Many of these people had been included in one of the previous studies that found a genetic association with clefting.  The researchers then examined the most promising variants in 665 families with an affected child.  All of the study subjects had European ancestry.

Two SNPs with significant associations were identified.  The relative risk of cleft lip with or without cleft palate was 1.36 for one copy of the A version of rs7078160, and 2.50 for two copies.  The relative risk was 1.38 for one copy of the G version of rs227731, and 1.91 for two copies. The results were published online yesterday in the journal Nature Genetics.

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

Both rs227731 and rs7078160 are located in regions of the genome previously associated with cleft lip and/or palate in animal models and in humans.

There is some evidence that cleft lip with and without cleft palate are two separate conditions, possibly with different genetic risk factors.  The authors of the current report did not find any difference between the effects of their most significant genetic associations, including rs227731 and rs7078160.  No association of these SNPs was found with cleft palate alone.

The researchers believe that together the previously described variants and these two newly identified SNPs account for a substantial proportion of the risk for sporadic cleft lip with or without cleft palate.  However, they think there are probably still additional genetic variants associated with this condition left to be found.

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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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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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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In the United States, prostate cancer affects about one in every six men.  Genomewide association studies aimed at finding common genetic variants associated with this common disease have been particularly successful. More than a dozen SNPs have been associated with prostate cancer, but researchers calculate that these variants represent only a tiny fraction of the genetic component of the disease.

To fill in the genetic gaps, researchers are turning to studies that include larger numbers of participants than ever before.  The hard work is paying off, as can be seen in four recent reports published in the journal Nature Genetics.  These analyses, based on the DNA of tens of thousands of men, have added at least 12 new variants to the roster of prostate cancer-associated SNPs.

One of the most striking features of these new studies is that they have identified two new SNPs on chromosome eight in a region known as 8q24.  Three other variants in this same region have already been linked to prostate cancer in both African American and European samples.  Other SNPs in the 8q24 region have been associated with breast, bladder and colorectal cancer.

(The new 8q24 SNPs as well as the others associated with prostate cancer are detailed in a table at the end of this post.)

The bounty of cancer-related SNPs in the 8q24 region is puzzling to scientists because there are no actual genes in this stretch of DNA.  The closest gene, MYC, is known to be involved in cancer, but so far there is no evidence that the cancer-associated 8q24 SNPs are affecting MYC. Future research will hopefully identify what these SNPs are doing and how they affect cancer risk.

Even though prostate cancer genomewide association studies have been fruitful, critics such as John Witte of UCSF argue that the findings may not be clinically useful (read his February Nature Genetics review of prostate cancer genomics here).

But that doesn’t mean that looking for variants associated with prostate cancer should be abandoned.  Finding SNPs associated with the disease could lead scientists to new treatments.

There is also the possibility of finding variants that don’t just predict whether someone is at risk for prostate cancer, but whether they are at risk for a particularly aggressive form of the disease. This could help doctors discriminate between those men whose cancers require immediate treatment and those who can avoid the side effects of surgery and radiation in favor of “watchful waiting.”

“There is clear clinical utility in identifying markers that can distinguish which prostate tumors will progress rapidly and be life-threatening versus those that are relatively latent and may not substantively impact a man’s health,” Witte writes.

As has been the case with most other studies looking for genetic variants associated with prostate cancer, none of the four new studies found an association between the identified SNPs and disease severity. Scientists have suggested that this indicates the studies are mainly finding variations associated with increased risk for the initiation of cancer. To find disease aggression-associated variants, more large studies will be needed, and researchers will need to focus on SNPs correlated with disease recurrence following treatment and/or mortality instead of just presence or absence of 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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Unlike the flu virus, which the body is generally able to fight off completely, infection with hepatitis C is often chronic.  That means for most of the three to four million people worldwide who are newly infected each year the virus will persist in the body, where it greatly increases risk for chronic liver diseases including cirrhosis and cancer. The only treatment currently available — an almost year long course of drugs — often causes severe side-effects. Worse yet, it fails in about half of all patients.

Last month, a study published online in the journal Nature showed that DNA variations in and around the IL28B gene influence whether a person chronically infected with the hepatitis C virus will fully respond to the standard treatment regimen. Now three new reports further support the importance of IL28B variations in the body’s response to hepatitis C, a finding that has implications for the future of hepatitis treatment and drug development.

An Australian group headed up by Vijayaprakash Suppiah analyzed the DNA of more than 800 people with European ancestry from Australia, the UK, Germany and Italy infected with hepatitis C.  They found that having one or two copies of the less-common G version of rs8099917, a SNP near the IL28B gene, doubled the odds that a person would fail to have a sustained response to treatment.

A group headed up by Yasuhito Tanaka studied 326 Japanese hepatitis C patients and also found that rs8099917 predicts whether or not a person will respond to treatment.  In this population, however, the effect was much greater.  Carrying a G increased the odds of treatment failure by at least twelve times.

“This SNP has such a strong association with response that, in combination with other parameters, genotyping it and other genetic variants should be a useful part of  clinical management,” write Suppiah et al., who along with Tanaka et al. published their results online this week in the journal Nature Genetics.

Another study, this one published online in Nature, found that variation near IL28B might be part of what allows a minority of people infected with hepatitis C to clear the virus naturally, without any treatment.

David Thomas and colleagues found that individuals with European or African ancestry were about three times more likely to spontaneously clear a hepatitis C infection if they carried two copies of the C version of rs12979860 than if they had CT or TT at this SNP.

Twenty-eight percent of the people with the CT or TT genotypes were able to fight off their hepatitis C infection without treatment, a number very close to the population average.  But 53% of those with the CC genotype were able to become naturally virus-free.

In a commentary published in Nature, Shawn Iadonato and Michael Katze express doubts about the importance of these new discoveries.

“Although these findings raise the tantalizing prospect of a more personalized approach to treating [hepatitis C] by tailoring treatment to patients who are most likely to benefit, the reality is more sobering,” they write.

Iadonato and Katze worry that testing for IL28B variations would not provide doctors with a straightforward yes-or-no answer to the question of whether a patient will respond to hepatitis C treatment.  This is because not all carriers of the advantageous versions of the variants clear the virus, nor do all patients lacking them fail to benefit from treatment.  Furthermore, they point out, there is currently no alternative hepatitis C treatment available.

What they do not consider, however, is how this new research may help change that. In a separate commentary in Nature Genetics, Thomas O’Brien suggests that the current findings could increase the interest in developing hepatitis therapies based on the protein encoded by IL28B, interferon-λ3.  He notes that an early clinical trial testing the effects of a related protein, interferon-λ1, has already had some success.  And certain properties of interferon-λs may cause them to have fewer side effects than current treatments.

O’Brien is still cautious about the findings linking IL28B variations to hepatitis C treatment response.  He says that more research in this area is needed in diverse populations and in people infected with different forms of hepatitis C.  He also stresses that researchers need to consider how these genetic findings fit in with other factors that affect treatment response, including age and gender.

Overall, however, his view is optimistic.  He concludes: “With these caveats, predictive models of HCV treatment response hold the potential to inform treatment decisions for millions of patients who are infected with HCV.”

(Rs12979860 was also described in the original paper linking IL28B to hepatitis C.  23andMe does not currently provide data for this SNP.  As pointed out in the previous Spittoon post on this topic, rs12980275 is very near to this SNP.  The A version of rs12980275 usually corresponds to the C version of rs12979860.  The other SNP discussed in this post, rs8099917, is located close to both rs12979860 and rs12980275.  23andMe customers can look up their data for rs8099917 using the Browse Raw Data feature.  Keep in mind that because all of these SNPs are so closely linked to each other, they are all probably representing the same effect.  More research will be needed to zero in on the exact variation(s) that are important for hepatitis C.)

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.

Map: PhilippN

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