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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In 2005 two well-known human geneticists, Francis Collins and Thomas Gelehrter, made a bet: Collins wagered that by the 2008 American Society for Human Genetics meeting, genomewide association studies would have led to the discovery of at least four “validated – not just guessed at” susceptibility variants for at least five common diseases.

Collins won his bet (and hopefully his beer) – by a margin of more than 200 variants.  According to the Human Genome Epidemiology Network, there have been 328 genomewide association studies published to date, and there is no sign of a slow down (as any devotee of SNPwatch knows). This type of research has clearly been successful. But how useful are the variants they identify?

There are two directions from which to consider this question. One is to ask whether the common variants found in genomewide association studies add to science’s understanding of the biology of various common diseases, as well as medicine’s ability to treat them.  The other is to ask whether the results of genomewide association studies have made it possible to predict individual genetic risk for various diseases.  Three opinion pieces, each with a different perspective, address these questions in the New England Journal of Medicine this week.

David Goldstein, director of the Center for Human Genome Variation at Duke’s Institute for Genome Sciences and Policy, doesn’t doubt the veracity of variants found in genomewide association studies.  But he does think that it’s time for geneticists to take a new approach.

“I believe attention should shift from genome scans of ever larger samples to studies of rarer variants of larger effect,” he writes in his NEJM commentary.

Goldstein says continued use of genomewide association approaches that look for common variants associated with common diseases and traits will ultimately lead to an unwieldy number of variants, each with vanishingly small effect sizes. For example, after making some assumptions he calculates that approximately 93,000 common variants could be needed to explain 80% of the population variation in height.

But variants with small effects can be biologically informative, argues Joel Hirschhorn, a Harvard genetics professor, in the second NEJM Perspective.  For example, genomewide association studies have identified variants associated with type 2 diabetes, high cholesterol and low bone density that are located in genes targeted by drugs already approved by the FDA for the treatment of these conditions.

“Each of the associated variants at a drug-target locus explains less than 1% of phenotypic variation in the population, demonstrating that small effect sizes do not preclude biologic importance,” he writes.

The discovery of variants with small effect sizes can also point scientists in the direction of new avenues for drug research, says Hirschhorn.  Genomewide association studies of age-related macular degeneration and Crohn’s disease have both revealed new mechanisms of disease that are now being pursued as therapeutic targets.

In the final NEJM Perspective, Peter Kraft and David Hunter from the Harvard School of Public Heath address genomewide association studies from the point of view of risk prediction.  They argue that while reliable risk predictions may be possible someday, testing for susceptibility based on common variants is currently premature for most conditions.  Like Goldstein, they note the small effect sizes associated with many of the common variants found so far.

“These factors suggest that many, rather than few, variant risk alleles are responsible for the majority of the inherited risk of each common disease….Estimates of risk based on established locus associations are therefore likely to change substantially in the next few years [as more variants are found],” Kraft and Hunter write.

Hirschhorn has a more optimistic view of the value of the variants identified through genomewide association studies.  He maintains throughout his article that the point of doing these studies is not risk prediction, but does say that it is likely that for some diseases, useful predictive information will emerge.  In fact, for some diseases the variants found to-date already give as much information to clinicians as other routinely used measures.

“For several diseases, associated variants already explain 10 to 20% or more of heritability, a magnitude that is similar to the proportion of risk explained by nongenetic tests in widespread clinical use (such as levels of low-density lipoprotein cholesterol or prostate-specific antigen),” Hirschhorn writes.

Hirschhorn goes on to argue that it is not how of much a disease’s genetics a variant or collection of variants explains, but how this information can shift the cost-benefit ratio of available clinical interventions.

“For diseases without potential therapies, even perfect prediction might not be clinically useful.  By contrast, for diseases with effective preventive measures that are too costly or for which the risk-benefit balance is nearly neutral, small increments in predictive power could help effectively target preventive efforts, with substantial clinical impact,” he writes.

Looking back at that 2005 bet between Collins and Gelehrter, it’s clear that not even the biggest names in the field could imagine just how far human genetics would come in such a short amount of time.  There’s no disputing that the study of common DNA variants has pushed science forward. And as new technologies and methods are developed, we’re sure to see even more progress.  We here at 23andMe hope to be a part of some of those new discoveries.

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Researchers have identified a genetic variation that may raise the risk for stroke by affecting brain cells’ ability to respond to injury.

Stroke is the third leading cause of death in the United States, striking almost 800,000 people each year. High blood pressure, high cholesterol, smoking, diabetes, obesity and a history of cardiovascular disease can all increase the risk of having a stroke, but studies of families and twins indicate that genes play a substantial role too.  So far, however, the genes underlying stroke risk in the general population remain undetermined.

Scientists combined data from several large studies comprising almost 29,000 people from the United States and the Netherlands to look for genetic variations associated with stroke risk. Their results, published online today in the New England Journal of Medicine, link a region of the genome not previously associated with stroke to increased risk in both black and white populations.

Strokes can be either hemorrhagic (caused by a broken blood vessel that bleeds into or around the brain) or ischemic (caused by a blood clot that blocks blood flow to the brain). Most strokes are the ischemic type.

Combined analysis of data from Caucasian study participants from the United States and the Netherlands revealed that the A version of rs12425791 is associated with a 1.29 times increased risk of ischemic stroke.  The SNP was also associated with an increased risk for ischemic stroke in a large African American study group – 1.42 times for each copy of an A.  Analysis of a smaller group of African Americans failed to yield a significant association between rs12425791 and stroke.

(23andMe customers can check their data for rs12425791 using the Browse Raw Data feature.)

The risk of stroke is almost doubled for African Americans compared to white Americans, and African Americans are more likely to die from stroke or complications from stroke than any other ethnic group.

Rs12425791 is located near the NINJ2 gene, which encodes a protein that has been implicated in nerve cell injury response in animal studies.  Several other SNPs in and around the NINJ2 gene showed modest association with stroke. The authors of the study suggest that SNPs affecting how much protein is made from the NINJ2 gene might influence the brain’s response when deprived of oxygen by a blood clot.

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Each time a doctor writes a prescription for warfarin (Coumadin®), a blood thinner given to about two million people each year in the United States, it’s a guessing game.  There is no “right” dose of the drug.  Everyone is different and it can take weeks of adjustment to find a patient’s ideal amount of the medication.  Too much puts the patient at risk for bleeding.  Too little can lead to clots and in turn, heart attack, stroke or even death.

In addition to clinical factors such as age, body size, other medications and ethnicity, genetic factors can affect a patient’s ideal dose of warfarin.  In 2007 the FDA added to warfarin’s label information about the importance of these genetic factors, but stopped short of directing doctors to carry out testing before prescribing the drug.  This may change, however, based on the results of a large international study published yesterday in the New England Journal of Medicine. The study shows that dosing decisions based on genetic information in addition to clinical data come significantly closer to the ideal dose for almost half of all patients.

Scientists from the International Warfarin Pharmacogenetics Consortium, comprised of research centers in Taiwan, Japan, Korea, Singapore, Sweden, Israel, Brazil, Britain and the United States, used the medical records and genetic information of about 4,000 patients who had been prescribed warfarin to develop a “pharmacogenetic” method for predicting the ideal dose. They then tested their method by applying it to the information from an additional 1,000 patients who had taken warfarin.

Compared to initial warfarin dosing decisions made with clinical data alone or based on a fixed starting dose of 35 mg per week for every patient, the pharmacogenetic method provided significantly better predictions of the final, ideal dose for many people.

“The greatest differences among the dose-prediction approaches were noted among patients whose stable therapeutic warfarin doses were 21 mg or less per week and among those whose stable doses were 49 mg or more per week, representing 46% of the cohort. These are the patients for whom an underdose or an overdose could have adverse clinical consequences,” the authors write.

The dosing method developed by the researchers did not provide a significantly better approximation for the 54% of patients whose ideal dose fell between 21 and 49 mg per week.

While the current study does show that genetic information can better predict the ideal dose of warfarin for a patient, it does not address whether this translates into less risk for bleeding or clotting. This question will be addressed by a soon-to-be-launched NIH-sponsored clinical trial called “Clarification of Optimal Anticoagulation through Genetics” (COAG).  This large study being conducted at 12 sites will evaluate how a gene-based dosing strategy affects a patient’s ability to maintain the correct level of blood thinning, the risk for bleeding problems, quality of life and cost of therapy.

“A better understanding of individual differences in the response, either positive or negative, to medicines should be an overarching goal for pharmacotherapy over the next decade. Pharmacogenetics has the potential to increase benefit and reduce harm in people whose drug responses are not ‘average’,” write Janet Woodcock and Lawrence Lesko, of the Center for Drug Evaluation and Research at the Food and Drug Administration, in an editorial that accompanies the study.

But, they warn, the move toward using genetic information to make prescription decisions must be made prudently.

“Given the expected volume of genetic information and the relative paucity of randomized, controlled trials involving marketed drugs, we need clear thinking about what is required for the adoption of pharmacogenetic testing.”

23andMe scientific advisor Russ Altman is a lead investigator for the International Warfarin Pharmacogenetics Consortium.

An article about the genetic influences on warfarin dosing is expected to be added to the Health and Traits section of 23andMe soon.  In the meantime, customers can use the Browse Raw Data feature to find out about their data as it relates to the study discussed in this post.  The study indicated that the ideal warfarin dose for people with the SNPs listed below may be lower than the average dose. As a reminder, 23andMe does not provide medical advice and this information should not be used to choose or adjust an already prescribed dose of warfarin.

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Every year, about half of the more than one million people in the United States who have a heart attack survive. But because the first heart attack increases their risk for another one, these people must make major adjustments in their lives to keep their hearts healthy in the future.

In addition to adopting a healthy diet, quitting smoking and losing weight, most people who’ve had a heart attack take medications to help further reduce their risk. Clopidogrel — sold under the trade names Plavix, Iscover, Clopilet and Ceruvin — is a drug commonly prescribed (often in combination with aspirin) to help prevent platelets in the blood from forming clots that can block blood flow to the heart.

Clopidogrel is converted into its active form once it is inside the body. But some people carry genetic variants that reduce the activity of an enzyme central to this conversion process, which in turn reduces the amount of active clopidogrel in the bloodstream and the effectiveness of the drug in preventing clots. Three reports published online this week – two in the New England Journal of Medicine and one in The Lancet – show that these genetic variants can increase the chances that a patient will suffer a second major cardiovascular event.

Jessica Mega and co-workers from Brigham and Women’s Hospital and Harvard Medical School in Boston tracked 1,477 subjects who had had unstable angina or a heart attack and were taking clopidogrel.

Their results, published in NEJM, showed that those people who carried one or more copies of a function-reducing variation in the CYP2C19 gene that (referred to as *2, *3, *4 and *5) had 1.53 times the risk of having a heart attack, stroke or dying from cardiovascular causes compared to non-carriers. The risk of a stent-blocking clot (in those patients who had stents implanted during angioplasty to keep their arteries open) was increased three-fold.

The second NEJM report, from researchers at several Paris hospitals led by Tabassome Simon, showed that in a group of 2,208 heart attack patients taking clopidogrel, carrying two CYP2C19 variants (any combination of *2, *3, *4, or *5) led to a 1.98 times increased risk of heart attack, stroke or death from any cause. Among the 1,535 patients who underwent angioplasty while in the hospital, having two function-reducing CYP2C19 variants increased the risk of cardiovascular events by 3.58 times.

Unlike the study from Mega et al, Simon and colleagues did not see an increased risk in those people with only one copy of a CYP2C19 function-reducing variant.

Finally, Jean-Philippe Collet and colleagues (also from Paris, France) followed the outcomes for 259 young (< 45 years old) heart attack patients taking clopidogrel. Their results, published in The Lancet, showed that having one or two copies of the CYP2C19*2 variant increased the risk of a second heart attack by 4.54 times. The risk of a stent-blocking clot increased 6.02 times.

Collet et al did not investigate the other CYP2C19 variants included in the other reports.

(23andMe customers can check whether they carry any of the CYP2C19 variants mentioned in these reports, except for CYP2C19*5, using the Browse Raw Data feature. See the table at the end of this post for more information.)

Although the magnitude of the effect of CYP2C19 variants was different in each report, all three did show that versions of the CYP2C19 gene that reduce its ability to activate clopidogrel also increased the risk of a second cardiovascular event in those patients who have already suffered one. Based on these results, both Simon et al and Collet et al suggest that genotyping patients might be a good alternative to the current practice of monitoring their platelet response to clopidogrel.

But in a commentary accompanying the report in The Lancet, Dr. Robert Storey of the Cardiovascular Research Unit at the University of Sheffield School of Medicine, UK, argues that testing platelet function in patients is faster than genotyping, and has the added benefit of finding patients who are not responding to clopidogrel due to factors other than CYP2C19 variants, such as age, diabetes, renal failure and cardiac failure.

“Genotyping of patients with acute coronary syndrome is not necessarily the appropriate solution without further work to validate such an approach,” he writes.

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Some families seem to have more than their fair share of illness. This is especially true in families with a propensity for autoimmune diseases, conditions that turn the body’s own infection-fighting cells against it.

Two autoimmune diseases in particular, type 1 diabetes and celiac disease, often cluster together in families, and even in individuals. The prevalence of celiac disease in people with type 1 diabetes is five to 10 times higher than in the general population.

A report published this week by the New England Journal of Medicine shows that shared genetic risk factors are at least partially to blame. According to experts, these findings could help scientists understand more about the underlying biology of both diseases.

The researchers, led by Professor John Todd from the University of Cambridge, tested nine SNPs known to be associated with celiac disease in 8,064 type 1 diabetes patients, 9,339 controls, and 2,828 families with a child affected by the disease.

Four SNPs showed a significant association with type 1 diabetes. Three of these were novel findings. The association of a SNP in the SH2B3 gene with both diseases was already known from previous work.

When the researchers looked in the other direction, testing 19 SNPs known to be associated with type 1 diabetes in 2,560 people with celiac disease and the same 9,339 controls, two significant associations with celiac disease were found.

The total number of cross-acting SNPs was brought to seven when the researchers found that a variation called CCR5delta32 is also associated with the risk of developing both type 1 diabetes and celiac disease. CCR5delta32 is most famously associated with resistance to HIV infection.

Of the variants associated with both type 1 diabetes and celiac disease in this report, all but two had an effect in the same direction – the riskier version for one disease was also riskier for the other.

But the SNPs in IL18RAP and TAGAP had opposite effects. The T version of each SNP increased the risk for celiac disease, but decreased the risk for type 1 diabetes.

A SNP having a different effect on the risk for different diseases is not unheard of. The A version of rs2476601 in PTNP22 increases the risk of type 1 diabetes and rheumatoid arthritis, but has shown to be protective for Crohn’s.

In an accompanying editorial in NEJM, Dr. Robert Plenge suggests that the SNPs identified in this study could theoretically be used to screen patients with one disease (i.e. celiac) to predict their risk of developing the other (i.e. type 1 diabetes). This type of screening, however, is controversial. Plenge also notes that because each SNP contributes only a small increase in risk, their use would not be likely to add much utility to current screening measures.

“The most important implication [of this kind of research] is likely to be the ability to define biologic pathways, many of which are unexpected, that cause disease. Over many years, such insight may lead to the development of novel therapies to treat, prevent, or even cure disease,” Plenge wrote.

23andMe currently reports data for eight SNPs for type 1 diabetes and one SNP for celiac disease in Health and Traits. Overlaps with this study are indicated with an asterisk in the first column. The report by Smyth et al report data for SNP rs45450798 in PTPN2, for which 23andMe does not provide data. We do, however, provide data for rs1893217, which is closely, but not perfectly, linked to rs45450798. The G version of rs1893217 is likely to be equivalent to the G version of rs45450798 as far as increasing risk, but the actual size of the effect may differ. Additional SNPs, including those in this report, will be added to the Health and Traits articles when our scientists are satisfied that the evidence meets our standards.

“Effect” refers to the change in odds of developing the disease per copy of the less common version of each SNP.

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It seems simple enough: if you eat only as many calories as you burn, you won’t pack on the pounds. Yet for many, balancing this equation is anything but easy. Obesity has become one of the most significant public health threats facing the United States and other developed countries. One-third of adults in the United States today can be considered clinically obese.

While lifestyle choices are certainly important, research has shown that genetics plays a significant role in determining a person’s propensity for being overweight or obese. One especially potent variant in the FTO gene has been consistently linked with weight in Europeans.

In a study of Scottish children published online yesterday by the New England Journal of Medicine, researchers suggest that this FTO variant may contribute to obesity by leading kids to chose foods that, pound for pound, pack a more powerful calorie punch.

[23andMe customers can see their data for an FTO SNP equivalent to the one used in this study by referring to the Health and Traits research report on obesity or using the Browse Raw Data feature. The T version of rs3751812 (equivalent to the A version of rs9939609 reported in this study) is associated with obesity]

Seventy-six kids between the ages of four and 10, selected from a larger study of 2,726 children who were having their height, weight, and FTO genotypes evaluated, also had their energy expenditure and food intake measured.

There was no difference in the number of calories burned while at rest between children who carried the higher weight-associated version of FTO and those who did not. Energy burned due to physical activity was actually higher for carriers than non-carriers. This suggests that the FTO variant isn’t affecting the basal metabolism rate or conferring a proclivity for a sedentary lifestyle.

There was also no difference in the total weight of the food ingested by the kids with the version of FTO linked to obesity. But these children did consume more calories than their non-carrier friends. The foods they chose during the test meals had “higher energy density” — they contained more calories per unit weight.

The authors note that most obesity disorders caused by defects in single genes (such as MCR4) affect eating behavior. These new results, and those of other studies (a few examples here, here, here and here), show that the common FTO variant is no different. It is unclear, however, whether FTO affects appetite regulation or the ability to sense how much food has been ingested.

In an accompanying editorial in NEJM, Dr. Rudolph Leibel says that although the proportion of obesity in the general population that can be attributed to variation in the FTO gene region is high, it’s probably still not enough to start using this SNP as a clinical screening tool.

But he goes on to say that in the not-so distant future more variants such as this one will be found and physicians will be able to assess a “score” based on maybe 15 to 20 genes to predict an individual’s risk for obesity.

“The important role that environment plays in enabling or resisting such susceptibility is clear evidence that such risk can be modified,” Leibel concludes.

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Most children have mastered the complexities of spoken language by age six or seven,. But about 5% of otherwise healthy children struggle with either expressing themselves, understanding what others are saying or both, a disorder known as specific language impairment (SLI).

In a report published online yesterday by the New England Journal of Medicine, researchers from the Wellcome Trust Centre for Human Genetics at the University of Oxford present evidence that a gene called CNTNAP2 is involved in specific language impairment.

“It has long been suspected that inherited factors play an important role in childhood language disorders,” Simon Fisher, senior author of the study, said in a statement. “But this is the first time that we have been able to implicate variants of a specific gene in common forms of language impairment.”

Several previous studies have linked broad regions of DNA with SLI, but there has yet to be any consensus on the true genetic underpinnings of the disorder.

The researchers narrowed in on the role of CNTNAP2 in SLI because it interacts with FOXP2, another gene implicated in the development of language skills. Some people with rare speech disorders have mutations in FOXP2, but variations in this gene have not been associated with more typical forms of language impairment.

In a study of children from 184 families with at least one child affected by SLI, the researchers found that each G at rs17236239 decreased the score on a test that measures the ability to hear and repeat nonsense words like “brufid” and “contramponist” by 5.53 points on average. Previous studies have indicated that this test is a good indicator of SLI.

Each G also decreased a child’s score on the standardized Expressive Language Score, which measures the ability to communicate through spoken language, by an average 3.21 points. Scores can range from 46 to 141 for the nonsense word test, and 50 to 150 for the expressive language test. Most children in the general population get a score between 85 and 115 on both.

(23andMe customers can check their data for rs17236239 using the Browse Raw Data feature.)

Variants in the same region of CNTNAP2 as rs17236239 have also been linked to delayed speech in children with autism. Some experts suggest that the different components of autism-spectrum disorders, such as communication problems, impaired social interaction, and repetitive behaviors, could be due to different genetic influences. Fisher and colleagues suggest that alterations in CNTNAP2 could be a shared mechanism for pure SLI and language problems associated with autism.

The research team plans to investigate whether variants of CNTNAP2 are linked to natural variations in linguistic abilities in the general population. They also plan to investigate other genes that interact with FOXP2.

“Genes like CNTNAP2 and FOXP2 are giving us an exciting new molecular perspective on speech and language development, one of the most fascinating but mysterious aspects of being human,” said Fisher. “This work promises to shed light on how networks of genes help to build a language-ready brain.”

In an accompanying editorial in NEJM, Karin Stromswold, who was not associated with the research, said that the findings of the British study and others like it could someday help tease apart the genetic and environmental factors that affect language and language disorders. Stromswold questioned, however, why others studies of SLI have never implicated the DNA region where CNTNAP2 is found, even when the same group of children was studied.

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Invasive aspergillosis (IA) is a common and life-threatening infection among bone marrow transplant patients caused by the fungus Aspergillus fumigatus. About 10% of bone marrow transplant recipients are affected by IA. An estimated 30% of those affected die within three months.

In June, researchers showed that a genetic variant in bone marrow recipients could increase their risk of developing IA almost six-fold . New research published online today in the New England Journal of Medicine shows that genetic variants in the bone marrow donor may also increase the risk of this potentially deadly infection.

Pierre-Yves Bochud and colleagues from the Fred Hutchinson Cancer Research Center and the University of Washington School of Medicine suggest that identifying IA-associated genetic variants in bone marrow donors could help doctors develop more effective prevention strategies for at-risk recipients.

Using a sample of 242 bone marrow transplant donor/recipient pairs, the researchers found that each T at rs4986791 in a bone marrow donor increased the risk the recipient would develop IA more than four times compared to donors with two Cs.

(23andMe customer’s can check their data for rs4986791 using the Browse Raw Data feature.)

A follow up study of 366 donors/recipients showed that this effect was seen only when the donors and recipients were unrelated. When a patient received a transplant from a relative, rs4986791 had no effect on the risk of IA. The researchers suggest that recipients of familial donations may require lower amounts of immunosuppressive drugs, thus decreasing their risk of all types of infections.

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“I feel like a fish with no water.”

That’s how the child in the public service announcement featuring a flopping, gasping goldfish describes what it feels like to have an asthma attack. The spot encourages parents of the close to nine million kids who suffer from asthma to take steps to decrease the number of attacks their kids have because, as the announcer says, “even one attack is one too many.”

Both environmental factors – things like mold, pollen, cold air and cigarette smoke — and genetic factors are thought to contribute to childhood asthma, a disease that causes more than 10 million missed days of school and leads to about two million trips to the emergency room each year.

Researchers are beginning to realize that asthma that strikes early in life may be a distinct disease from cases that set in later. In 2007, a genomewide association study linked several related SNPs in a region of chromosome 17 specifically to childhood asthma. New research published online today in the New England Journal of Medicine confirms these genetic findings and adds a new twist: the SNPs have an effect only in kids exposed to tobacco smoke.

(23andMe customers can check their data for one of the chromosome 17 SNPs associated with childhood asthma in Research Reports.)

Bouzigon and colleagues studied several hundred French families and found a number of SNPs linked with asthma on chromosome 17, just as in earlier studies. The SNPs were associated only with asthma that began at age four or younger.

Like previous researchers, Bouzigon et al could not determine exactly how the SNPs are related to childhood asthma risk; but they could clearly show that the variants’ effects are triggered by exposure to tobacco smoke. The researchers found that the overall risk of early-onset asthma was increased at least 1.7-fold for people with two risky copies of any of the SNPs compared to those with none or only one. But when they took smoking into account, they saw that children with two risky copies of any of the SNPs who were also exposed to tobacco in utero, during infancy or both actually had risk at least 2.3-fold higher than those with the more favorable genotypes. The SNPs had no statistically significant effect among children who were not exposed to tobacco smoke early in life.

In an accompanying editorial in NEJM, two researchers not involved in the study — John Holloway and Gerard Koppelman — say that the influence of early life events in the development of asthma is well supported, and that the interaction of genes and tobacco smoke seen by Bouzigon and colleagues “further highlights the detrimental effect of such early life exposure on respiratory health.”

But, say Holloway and Koppelman, the importance of the exact timing of exposure to tobacco smoke is not clear, as Bouzigon et al could not differentiate between prenatal and postnatal exposure.

Although more research will be needed to confirm the results in this new report, Holloway and Koppelman think that as more is learned about how chromosome 17 variants affect asthma risk, this knowledge may help physicians better treat the disease.

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