Our SNPwatch posts here at The Spittoon are one of our most exciting features. They give our customers the opportunity to connect their genetic data to the newest discoveries, often within just hours of a study’s publication.

Looking ahead to 2009, we can only begin to imagine the exciting discoveries that will be made in genetics. In the meantime, here are a few of our favorite SNPwatches from 2008:

SNPs That Affect Drug Response
We reported on several studies this year that showed the importance of genetic variations in determining how different people react to certain medications.

• A report in Nature Genetics showed that some women with a particular version of a SNP in the NQO1 are less likely to survive breast cancer after treatment with the commonly used chemotherapeutic epirubicin.
• A study by the SEARCH Collaborative Group found that a version of one SNP is associated with an increased risk for myopathy (muscle pain and/or weakness) in people taking cholesterol-lowering drugs called statins.
• Mayo clinic researchers found that the weight loss drug sibutramine (Meridia) is effective only in people with specific versions of three different genes.
• And just this month we brought you news of three studies that showed that a genetic variant known to affect the metabolism of the anti-clotting drug clopidogrel (Plavix) also affects heart attack patients’ risk of a second major cardiovascular event.

Shared SNPs
Sometimes multiple conditions strike the same person or run in families. Several studies published this year showed that shared genetic risk factors may be part of the reason why.

• Obesity is a known risk factor for many cancers. Researchers found that a variant of adiponectin, a hormone released by fat cells, can increase the risk of developing colorectal cancer.
• Other researchers found variants that affect the risk of developing both type 1 diabetes and celiac disease, two autoimmune diseases that tend to cluster together. One of these shared variants is also associated with HIV resistance.
• Finally, a report published this month in the Proceedings of the National Academy of Sciences showed that a single genetic variant can make a person prone to greater indulgence in both smoking and drinking.

SNPs Associated with Risk Factors for Disease
Several studies this year looked beyond disease itself and instead found associations between SNPs and traits known to be risk factors for disease.

• One study found an association between several SNPs and fasting plasma glucose, a measure of how well a person’s body can control blood sugar levels – a process that goes awry in diabetes.
• Another research group reported SNPs associated with glycated hemoglobin levels, a measure of long-term blood sugar control and another factor associated with the risk of developing diabetes.
• The findings of three papers published in Nature Genetics roughly doubled the number of SNPs associated with blood levels of cholesterol and triglycerides, important risk factors for cardiovascular disease.
• And finally, in a study that looked at behavior instead of metabolic markers, researchers found that a variant in the FTO gene known to increase the risk for obesity affects food choices in children, pushing them towards foods denser in calories.

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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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