Researchers have identified several genetic variations associated with the timing of a baby’s first tooth and the number of teeth at age one. The results, published recently in the journal PLoS Genetics, could be important for understanding more about human health than just this rite of passage all babies must go through.

Nascent teeth form in the womb, but for most babies the first one doesn’t poke through the gums until sometime between four and seven months of age. Some little ones, however, begin teething as early as three months, while others may take a year or more to sprout their first pearly whites. Although the genetic bases for many syndromes involving serious problems with tooth formation have been discovered, until now not much work has been done to understand how our DNA impacts the normal variation in teething seen in the population.

British and Finnish researchers analyzed the DNA of about 6,000 people (approximately 1,500 from the U.K. and 4,500 from Finland) who had been followed by epidemiologists since early in their mothers’ pregnancies. Genetic variants in 10 different regions of the genome had at least a suggestive link to age at first tooth eruption and/or number of teeth at one year. Those SNPs with statistically significant associations with at least one of the traits are shown in the table below.

*= association not significant for tooth eruption; **= association not significant for number of teeth at age one.

Subjects are classified by the number of delayed tooth eruption alleles. SNPs are chosen so that they had the strongest signal for number of teeth at each locus. Mean time of first tooth eruption is plotted in red and number of teeth by the age of one year in black. The bars represent the number of individuals for each count of ‘delayed tooth eruption’ alleles. The line through points is a linear regression fit. doi:10.1371/journal.pgen.1000856.g002

Much as has been the case for genetic associations with height, another highly heritable and complex human trait, the variations the researchers linked with teething characteristics explain only a tiny fraction—about 3-4%—of the total variance seen in the population. More studies, with larger samples, will be needed in order to identify more SNPs, including those with smaller effect sizes and rare variants.

Based on the significant SNPs listed above, the authors defined a summary statistic called the “delayed tooth eruption measure,” which is calculated by adding up how many copies of the “delayed” version of each SNP a person carries. For women the total possible is 10 (two copies of each of five SNPs). Because one of the SNPs is on the X chromosome, for men the total possible is nine.

Based on the Finnish sample, the researchers calculated that individuals with a delayed tooth eruption measure of eight or more have an average of 1.5 fewer teeth at 12 months of age, and later tooth eruption by 1.1 months, compared to individuals with a score of three or less.

The researchers also evaluated whether or not any of the SNPs found in their study of infant teething were associated with the need for orthodontic treatment by age 31 in their Finnish sample. The only significant finding was a SNP that showed only suggestive evidence for an association with timing of first tooth eruption and number of teeth at age one (i.e., it is not in the table above). Each G at rs6504340 increased the odds of requiring orthodontic treatment by 1.35 times.

All of the SNPs identified in this study are in or around genes known to have roles in organ formation, growth and development, or cancer. The authors suggest that studies of teething and other aspects of infant development may have far reaching implications.

“The discoveries of genetic and environmental determinants of human development will help us to understand the development of many disorders which appear later in life. We hope also that these discoveries will increase knowledge about why fetal growth seems to be such an important factor in the development of many chronic diseases, ” said Professor Marjo-Riitta Jarvelin, the study’s senior author, in a press release.

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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Atrial fibrillation (AF) is the most common irregular heart rhythm, affecting one in four people over the age of 40. While not usually life-threatening on its own, individuals with the condition are at increased risk of stroke and heart failure. AF appears most frequently in older, male individuals with a history of obesity or cardiovascular problems, but some people develop it at a young age and with no obvious heart disease. This type of AF, known as “lone” AF, tends to run in families but is otherwise difficult to diagnose.

Previous studies covered by The Spittoon have linked common genetic variants to AF, but these studies have focused mainly on the typical, later-onset type of AF. Led by Patrick Ellinor and Stefan Kaab, a group of researchers from the United States and Europe investigated the genetic basis for lone AF in a group of about 1,300 people of European ancestry with the condition and more than 12,000 people without AF. Their study, published this week in Nature Genetics, connected the genetic variant rs13376333 with increased risk of lone AF.

In their analysis, each copy of the T version of rs13376333 increased the odds of lone AF by 1.52 times compared to two copies of the C version. The T version was also associated with an increased risk of typical AF, but the effect was smaller – only 1.13 times higher odds of having the condition for each copy.

(23andMe Complete Edition customers can check their data for rs13376333 using the Browse Raw Data feature.)

The variant is located near KCNN3, a gene that codes for an ion channel responsible for controlling the movement of potassium in and out of cells. KCNN3 ion channels in particular are found in “excitable” tissues such as the brain and heart. In mice, abnormalities in the behavior of the KCNN3 gene have been associated with increased blood pressure, but the exact role of KCNN3 in the human heart is unclear. Further research is needed to explore whether KCNN3 may have therapeutic applications for treatment of AF.

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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People chronically infected with the hepatitis C virus currently have only one treatment option:  a combination of polyethylene glycol (PEG)-ylated interferon alpha and ribavirin (RBV).   Not only does this drug regimen fail to eradicate the virus in about half of all patients who receive it, but even when it does work the side effects can be so bad that treatment has to be scaled back or abandoned altogether.

In up to two-thirds of all hepatitis C patients, RBV treatment leads to the destruction of red blood cells and a decrease in the amount of oxygen that can be transported throughout the body, a condition called hemolytic anemia.  New research, published online yesterday in the journal Nature, shows that genetic variants that cause a normally benign enzyme deficiency actually offer some protection against this condition.

Duke researchers Jacques Fellay, Alexander Thompson and Dongliang Ge, along with colleagues from the Schering-Plough Research Institute and the Johns Hopkins School of Medicine, studied about 1300 European-Americans, 200 African-Americans, and 100 Hispanics receiving hepatitis C treatment.  The patients had their hemoglobin (the oxygen-carrying protein in red blood cells) levels measured at the beginning of their treatment and at the four-week mark, the point when many patients must begin treatment to stimulate red blood cell production due to RBV-induced anemia.  The researchers also analyzed the patients’ DNA to look for genetic variants associated with hemoglobin level changes.

Several variants on chromosome 20 showed a significant association with maintenance of good hemoglobin levels after RBV treatment.  Deeper analysis of this DNA region revealed that the effect could be traced to two variations in the ITPA gene.

The ITPA gene encodes an enzyme that helps breakdown a substance called inosine triphosphate in cells.  The less common versions of the two variations the researchers identified (A at rs1127354 and C at rs7270101) both reduce the function of the ITPA enzyme.  In most people this isn’t a problem.  For people taking drugs called thiopurines, which are used to prevent organ rejection in transplant patients and to treat leukemias and autoimmune disease, reduced ITPA activity may lead to toxicity.  What the new study found is that for people receiving treatment for hepatitis C, less ITPA enzyme function is actually a good thing.

Of the people in the current study predicted to have less than one-third of the normal ITPA activity due to their genetics, none ended up with hemoglobin levels below the level traditionally set as a threshold for RBV dose reduction.  Of those with normal ITPA levels, 11.7% had their hemoglobin levels dip into the danger zone.

(23andMe does not currently provide data for rs7270101.  But we do provide data for rs1127354.  Complete Edition customers can use the Browse Raw Data feature to see their genotype for this SNP. Each SNP was shown to have an independent effect on hemoglobin levels in the face of RBV treatment.)

More research into the genetics of RBV-induced anemia will be needed.  Although the exact effect varied among the different populations studied, the researchers estimate that about 20-30% of the variability in hemoglobin level reduction in response to RBV treatment was explained by rs1127354 and rs7270101.  There was no significant association between these SNPs and the efficacy of hepatitis C treatment.

(Other SNPs have been associated with treatment outcomes; see here and here in the Spittoon, or the 23andMe Response to Hepatitis C Treatment Drug Response Report.)

Because having low levels of ITPA enzyme activity does not seem to cause any problems for most people, the authors suggest that drugs that inhibit this enzyme could be developed so that people receiving RBV treatment for hepatitis C could be protected against anemia, even if they do not carry the protective genetic variations.

Illustration of ITPA protein structure: Emw

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 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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There’s no doubt that blood saves lives.  According to the Red Cross, in the United States alone about five million people need a total of 14 million pints of blood each year.  That’s 38,000 pints every day.

But transfusions are not without their dangers.  Among them is transfusion-related acute lung injury (TRALI), a rare but potentially life-threatening condition that happens when there is a clash between donor and recipient blood.  TRALI is one of the major causes of transfusion-association deaths in the developed world.

New research, recently published in the journal Nature Medicine, suggests that many cases of TRALI are due to a difference at just one genetic variation between donor and recipient.  This finding could someday enable screening before a transfusion is done, allowing doctors to reduce the risk of TRALI.

One reason TRALI happens is that a donor’s blood contains antibodies that recognize something in the recipient’s blood as an enemy.  These donor antibodies mount an attack that sets off a chain reaction of immune responses in the recipient’s body, leading to lung injury.  Several triggers for this type of TRALI have been identified.  One of these, the HNA-3 antigen, has repeatedly been associated with severe and fatal TRALI reactions.

HNA-3 comes in two versions: HNA-3a and HNA-3b.  A person whose body expresses only the HNA-3a version can make antibodies against the HNA-3b version if he or she is exposed to it somehow.  Likewise, a person whose body expresses only the HNA-3b version of the protein can end up with antibodies against the HNA-3a version. Someone who expresses both HNA-3a and HNA-3b, as a result of inheriting a different version from each parent, won’t make antibodies against either version.  For reasons that aren’t really understood, only antibodies against the HNA-3a version are relevant when it comes to TRALI.

The most common route of exposure to foreign versions of the HNA-3 antigen is childbirth.  A woman can be exposed to her child’s blood, and if it contains a different version of HNA-3 than her body is used to, she might produce antibodies.  The likelihood that a woman will have antibodies against HNA-3 increases with each birth.

The new research found that the different versions of HNA-3 are due to SNP rs2288904 in the SLC44A2 gene.  Someone who is GG at this SNP will express only HNA-3a.  Someone who is AG will express both the HNA-3a and HNA-3b version.  Finally, someone who is AA at rs2288904 will express only HNA-3b.  The first two genotypes (GG and AG) represent about 95% of the population with European ancestry.  These are the people who are at risk for TRALI if they receive blood from a donor who is part of the 5% of the population that has AA at rs2288904.

(23andMe Complete Edition customers can check their data for rs2288904 using the Browse Raw Data feature.)

Confused?  Here’s an example from my own family that will hopefully make things more clear:

The authors of the new study suggest that their new findings can be used to develop a large-scale screening program that could reduce the risk of TRALI.  Blood donors could be genetically screened to find those who are capable of producing antibodies against HNA-3a (i.e., they are AA at rs2288904).  Alternatively, the new genetic information could help scientists create artificial HNA-3a antigens that could be used in the lab to screen donated blood directly.

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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Researchers have identified another region of the genome associated with childhood asthma, a condition that affects more than seven million American kids.

Analysis of DNA from about 1,700 children with asthma and 3,500 controls, all of European ancestry, identified several genetic variations on chromosome 1 associated with the risk of developing asthma.  Many of these same SNPs were then also found to be associated with risk for asthma in a sample of more than 1,600 African American children with asthma and 2,045 controls.  All of the newly identified SNPs are located near the gene that encodes DENND1B, a protein known to be involved in the body’s response to foreign particles.

“Many of these particles are well-known triggers of asthma.  In asthma, patients have an inappropriate immune response in which they develop airway inflammation and overreaction of the airway muscle cells,” explained Hakon Hakonarson, director of the Center for Applied Genomics at The Children’s Hospital of Philadelphia and the senior author of the study, in a press release.

The chromosome 1 variations identified by the researchers affected the odds of childhood asthma in different ways depending on ethnicity.  Versions of the SNPs associated with increased risk in African Americans were associated with decreased risk in the European sample.  This is not unusual in genetic studies, and often reflects differences in population history.

One of the most promising SNPs is rs1775456.  In African American children, each copy of the less common G version of this variation was associated with 1.86 times increased odds of asthma.  In children with European ancestry, each G was associated with 0.75 times odds of the condition.  The results were published recently in the New England Journal of Medicine.

(23andMe Complete Edition customers can view their data for rs1775456 using the Browse Raw Data feature.)

Hakonarson suggests that his team’s finding that DENND1B has a genetic link to asthma could lead eventually to the development of new types of treatments.

“Other asthma-related genes remain to be discovered, but finding a way to target this common gene variant [found in the study] could benefit large numbers of children,” he said.

Previous research linked genetic variants on chromosome 17 with the risk for childhood asthma in Europeans.  Some of these studies suggested that these variants have an effect only in children who are exposed to tobacco smoke.  More research will be needed to work out the details, but the importance of chromosome 17 in asthma was further supported by the current study, which replicated the previous findings in addition to identifying the new variants on chromosome 1.

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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Leprosy is a chronic, disabling disease caused by a bacterium (Mycobacterium leprae) that infects only humans and armadillos. The disease affects the skin and peripheral nerves, leading to sores, numbness in the limbs, muscle weakness, and, in severe cases, disfiguring nodules on the skin. Known since biblical times, leprosy was highly stigmatized until the latter part of the 19^th century, when the Norwegian doctor Gerhard Hansen discovered that it was caused by a microorganism.

Although multi-drug therapy has cured millions of people of leprosy in recent decades, hundreds of thousands of new cases still occur per year, mostly in developing countries. Finding a way to eradicate the disease is therefore considered important for reducing the number of preventable disabilities worldwide.

Because Mycobacterium leprae is specific to humans and cannot be grown in lab dishes, research into factors influencing disease susceptibility and clinical outcomes has been limited. But the host environment as well as the bacterium itself can affect the course of the disease; in other words, human genetic factors may play an important role in determining who is more susceptible to infection. Since leprosy has been shown to cluster in families, scientists suspect that much of the variability in disease susceptibility and symptoms stems from diversity in individual human immune systems rather than differences between and within strains of the bacteria.

In a new study published today in New England Journal of Medicine, a team of researchers reports new human genetic factors associated with susceptibility to leprosy in Asians. Led by Fu-Ren Zhang of the Shangdong Academy of Medical Sciences in China and Jian-Jun Liu of the Genome Institute of Singapore, the scientists tested 93 variants across an estimated 50 genes in 3254 Chinese individuals with leprosy and 5955 Chinese individuals without the condition. Their analysis identified variants in seven of these genes to be significantly associated with leprosy.

“The discovery of these genes is a major breakthrough for research in leprosy and infectious diseases in general, and will be significant in the early diagnosis and development of new treatments,” said Dr. Liu in a press release.

The strongest of the associations were rs602875 in HLA-DR-DQ, rs3764147 in C13orf31, and rs9302752 in NOD2. In addition, some of the genetic variants were more strongly associated with a form of leprosy that results in more severe symptoms, known as the multibacillary form. These included rs9302752 in NOD2 and the variant rs1491938 in LRRK2.

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

Altogether, five of the seven genes identified in the study could be shown to interact biologically in the context of immune response to infection. Two of these five genes, NOD2 and TNFSF15, harbor genetic variants that are also associated with Crohn’s disease (see 23andMe’s report on this condition). Crohn’s manifests some common features with leprosy at the cellular level and other researchers have suggested that mycobacterial infection may be a risk factor for Crohn’s. The findings reported by Zhang and Liu and their colleagues provide additional evidence for shared disease mechanisms between Crohn’s disease and leprosy and may increase the range of treatment options for both conditions.

Variants significantly associated with leprosy in individuals of Asian ancestry

* As reported on the 23andMe website through the Browse Raw Data feature.

** Effect only applicable to the multibacillary form of leprosy. LRRK2 is better known as a susceptibility gene for Parkinson’s disease (see 23andMe’s report on this condition). Interestingly, PARK2, another gene linked to Parkinson’s, was associated with leprosy in earlier studies. The reason for the connection between Parkinson’s and leprosy is unclear, though researchers have speculated that some of the same treatments may be effective for both conditions.

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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Multiple sclerosis (MS) afflicts the central nervous system, causing unpredictable and varying symptoms that differ from person to person. About one in 700 people in the United States is affected by the disease. Although there is currently no cure for MS, there are treatments that can slow the progression of the disease and enhance the quality of life for people who have this condition.

Researchers have identified several genetic variants in the HLA region of the genome –an area containing many genes involved in immune system function – that seem to affect MS symptoms, disease severity, and response to treatment. One of these variants is in the HLA-DRB1 gene. Known as HLA-DRB1*1501, this variant is associated with increased risk for MS, though exactly how it is involved in development of the disease is unclear.

In a report published online today in the journal Archives of Neurology, a team of researchers led by Drs. Madeleine Sombekke and Chris Polman of Vrije University in Amsterdam uncovered a clue which may elucidate the connection between the HLA-DRB1*1501 variant and multiple sclerosis. They analyzed *1501 and other genetic variants in 150 Dutch individuals with multiple sclerosis to see if any of the SNPs were associated with variation in brain and spinal cord lesions.

One SNP in particular, rs3135388 (used as a proxy for HLA-DRB1*1501), was associated with spinal cord lesions. People carrying at least one copy of the A version of rs3135388 had significantly more spinal lesions and had more segments of the spinal cord affected than people with two copies of the G version.

(23andMe Complete Edition customers can check their data for rs3135388 using the Browse Raw Data feature.  This SNP is also part of the Multiple Sclerosis Research Report available to Health and Complete Edition customers.)

MS is believed to be an autoimmune disorder – wherein the immune system attacks the body’s own cells rather than foreign invaders – and so it makes sense that genetic variants in immune system genes would influence the course of the disease and its clinical features. HLA genes, in particular, encode proteins that contribute to self vs. non-self immune recognition. Previous studies have proposed a link between HLA-DRB1*1501 and disease severity. Since lesions on the spinal cord are often used to diagnose MS and the degree of disability, Sombekke’s team suggests that the association of HLA-DRB1*1501 with spinal cord lesions might help explain its relationship with severity of 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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