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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As anyone who indulges in both smoking and drinking can tell you, the two are a natural — if unhealthy — combination. Now research suggests that some people possess a single genetic variation that makes them prone to greater indulgence in both vices — and the attendant health risks.

Several research papers published in the last year or so show that a cluster of genes on chromosome 15 encoding nicotinic receptors, which regulate the brain’s response to nicotine, are related to smoking behavior. We cite one of those papers in the 23andMe Health and Traits entry for Nicotine Dependence — it shows that on average, smokers with an A at both copies of the SNP rs1051730 light up once more per day compared to those with the AG or GG genotype.

The authors of the new study, which appears in the latest issue of the Proceedings of the National Academy of Sciences, noted that connection between chromosome 15 and nicotine dependence. They also observed the fact that twin studies have established a genetic connection between smoking and alcohol abuse and that experiments show mice consume less alcohol when treated with a drug that blocks nicotinic receptors.

So the researchers, who were from the Ernest Gallo Clinic and Research Center in Emeryville, Calif., and the University of California, San Diego, reasoned that the very same genetic variations recently associated with smoking behavior could influence drinking as well. To test that hypothesis, they genotyped 367 participants aged 18 to 29 and tested them on various measures of alcohol response. Those with an A at both copies of rs1051730 were better able to maintain their coordination after drinking a given amount of alcohol and reported feeling less drunk compared to those with either the AG or GG genotypes. The researchers also found a second SNP nearby on chromosome 15 — rs8034191 — that was also linked to alcohol sensitivity. In that case, having a C at both copies of the SNP decreased a person’s response to alcohol. 23andMe customers can check their own genotypes at both SNPs using the Browse Raw Data feature.

Some people might consider it good news to learn that they have a genetically enhanced ability to hold their drink. But a reduced response to alcohol increases a person’s risk of alcohol abuse. So in addition to causing people who do smoke to light up more often, this particular genetic signature also appears to threaten health by increasing a drinker’s chances of developing problems with alcohol.

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Not all alcoholics are created equal. People differ in why they drink, how they drink and what effects drinking will have on their health and relationships.

A key biological component of the variability in alcoholism may be in the control of signaling by serotonin, a brain chemical that carries messages between nerve cells and mediates the rewarding effects of alcohol.

Scientists at the University of Virginia have found that a variation in the serotonin transporter gene, which regulates serotonin levels, is associated with drinking intensity. The results, which will appear in the February 2009 issue of Alcoholism: Clinical and Experimental Research, were published online yesterday.

Senevirante et al tested six variations in the serotonin transporter gene for association with drinking intensity in 275 alcoholics seeking treatment — 165 were Caucasian and 110 were Hispanic. Women made up 21.5% of the sample.

In the Caucasian sample only, the researchers found that having one or two copies of a C at rs1042173 led to less intense drinking, defined as number of drinks per drinking day. There was no difference in number of drinks averaged over 90 days. People with the AA genotype drank an average of about 11 drinks per drinking day, while those with the AC or CC genotype drank about eight and a half.

(23andMe customers see their data for rs1042173 using the Browse Raw Data feature)

Previous research has linked a separate variation in the serotonin transporter (5-HTTLPR) with alcohol dependence, but results have been conflicting.

The study’s authors point out that in all cases, the number of drinks people had exceeds the threshold for what is considered heavy drinking (five or more standard drinks per day for men and four or more for women). They also note that their study looked only at alcoholics seeking treatment, who may not be representative of alcoholics in general.

In the future, the researchers say they hope to investigate whether rs1042173 can be used to provide more effective treatment for alcoholism by predicting whether medications that affect the serotonin system will work for an individual.

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