Although environment plays a major part in addiction — you can’t get hooked on something you’ve never tried — genetics plays a substantial role in determining whether a person who does use a drug will become addicted to it.

A few DNA variations have been identified that seem to increase the odds a person will become addicted to a specific drug. But twin studies suggest that there might be genes influencing addiction in general.

Xiang Chen and colleagues at Yale and Princeton set out to find some of these genes by analyzing the genetic data from several cohorts of people previously studied for addictions.  The researchers’ approach was to look for variations found more frequently in people addicted to at least two out of six categories of substances: nicotine, alcohol, marijuana, cocaine, opiates and other drugs.  Their results, published online this week in the Proceedings of the National Academy of Sciences, reveal a significant association between addiction and variations in a gene, PKNOX2, previously associated with alcohol dependence in mice.

The strongest signal was seen with rs12284594.  In white women, each copy of a G at this SNP corresponded to 1.77 times increased odds of being addicted to two or more substances.  The association with addiction of this and other SNPs in the PKNOX2 gene was also seen in the white men and black men and women in the study, but the findings were not statistically significant.

(23andMe customers can check their data for rs12284594 using the Browse Raw Data feature.)

The association of rs12284594 with addiction did not hold when the researchers looked at individual substances separately.

“This suggests that substance dependence or addiction as a whole has different risk genes compared to any single addiction outcome,” the authors write.

The authors admit that there are weaknesses in their study.  For example, people addicted to two or more substances might just have more access to drugs — not a biological predisposition to addiction.  Moe research in this area will definitely be needed.

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.

More Spittoon Posts About Addiction and Substance Dependence:
SNPwatch: Genetic Variation May Make It Harder For Expectant Moms To Quit Smoking
How A Person Smokes Might Affect Lung Cancer Risk
SNPwatch: Two Vices, One SNP — Drinking and Smoking Behavior Both Linked to Nicotine Receptor Genes
SNPwatch: Focusing on a Gene Variant that Might Help Counter Cigarette Cravings
SNPwatch: “Environment” also genetic?
SNPwatch: Genetic Variant Linked to Drinking Intensity in Alcoholics
SNPwatch: Next Year It’s Martinelli’s…
SNPwatch: Unlikely Gene May Contribute To Cocaine Dependence and Paranoia

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For many women, finding out they’re pregnant is the kick in the pants they need to quit smoking.  But for some, a genetic variation may stand in their way.

The SNP rs1051730 is located in a cluster of genes on chromosome 15 that are involved in regulating the brain’s response to nicotine. Studies have already shown that the SNP is associated with nicotine addiction. Now a new report, published online last week in the journal Human Molecular Genetics, suggests that the effect of this variation is strong enough to overcome the maternal instinct and social pressure to protect one’s unborn child from the harmful effects of cigarette smoke.

British researchers studied 2,474 women who smoked regularly before becoming pregnant.  When questioned about smoking during their first trimester, 31% of the women with two Gs at rs1051730 had kicked the habit, compared to only 21% of the women with two As.  During the third trimester, 47% of women with two Gs were smoke-free, while only 34% of women with two As were.

Overall, after adjusting for pre-pregnancy smoking quantity, the researchers calculated that each A at rs1051730 increases a woman’s odds of continuing to smoke throughout her pregnancy by about 1.2 times.

The authors say their results show how genes can influence what is perceived by many to be a matter of self-control, but that “it’s in my genes” shouldn’t used as an excuse to avoid giving up smoking during pregnancy.

23andMe customers can check their data for rs1051730 using the Browse Raw Data feature.  This SNP is also featured in the Nicotine Dependence Research Report.  For more information, check out the following Spittoon posts related to this SNP:

• SNPwatch: Genetic Variation Linked to Smoking and Lung Cancer Might Also Raise Risk for COPD
• How A Person Smokes Might Affect Lung Cancer Risk
• SNPwatch: Two Vices, One SNP — Drinking and Smoking Behavior Both Linked to Nicotine Receptor Genes
• SNPwatch: Focusing on a Gene Variant that Might Help Counter Cigarette Cravings
• SNPwatch: “Environment” also genetic?

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A new discovery could someday help identify smokers at risk for chronic obstructive pulmonary disease (COPD), the fourth leading cause of death in the United States.

More than 12 million people in the U.S. have been diagnosed with COPD, and another 12 million may have the condition and not know it.  These people have difficulty breathing due to excessive inflammation in their lungs that has narrowed their airways.  The cause of the inflammation is usually prolonged exposure to an inhaled irritant, most often cigarette smoke. Nine out of ten COPD deaths can be attributed to smoking.

But even though most people with COPD are current or former smokers, not every smoker gets COPD.  Only about 20% will develop the disease, suggesting that there might be genetic factors that make some smokers more susceptible than others. New research, published yesterday in the journal PLoS Genetics, suggests that variation in a genetic region on chromosome 15 previously linked to nicotine addiction, lung cancer and peripheral artery disease might also increase the risk for COPD.  In light of the mounting evidence for the importance of this stretch of DNA, the authors of the new report suggest that genetic screening of smokers in order to find those at the highest risk may be an attractive interventional strategy.

Sreekumar Pillai, a scientist at GlaxoSmithKline, and colleagues from several research institutions studied a total of more than 5,000 people with European ancestry and found that each A at the SNP rs1051730 on chromosome 15 increased odds of COPD by about 1.3 times.  They also found that each C at SNP rs8034191 increased the odds of COPD by about 1.4 times. The two SNPs are very close to each other and probably both mark the same variation affecting COPD risk, although the authors did not test this.

[23andMe customers can check their data for rs1051730 and rs8034191 using the Browse Raw Data feature.  Keep in mind that because the SNPs are closely linked, having the same version of both (either non-risk or risk) is expected.  A riskier version at both does not indicate doubled risk.]

Research has shown that in smokers, each A at rs1051730 is associated with smoking one more cigarette per day.  Whether rs1051730 is linked to lung cancer and peripheral artery disease because of or in addition to its effects on smoking has been controversial.  The authors of the current study say that while their data does not allow them to solve this dilemma with regard to the effects of the chromosome 15 SNPs on COPD, several aspects of their study indicate that the genetic variation has a direct effect on the disease, independent of smoking behavior.

The authors do note, however, that in some subsets of their study population the effect of the riskier versions of the genetic variations was greater in current smokers compared to former smokers.  This could mean that people who have a harder time quitting are more likely to develop COPD.  Alternatively, it could be the case that some people are at higher risk for COPD if they continue to smoke.

The researchers also found evidence for variations contributing to COPD on chromosome 4, although the results were not statistically significant. However, this same region of DNA was correlated with lung function in a different report in same issue of PLoS Genetics.  Both research groups pointed out that the nearest gene to the chromosome 4 variations they identified is involved in lung development, suggesting that future research targeting these variations might reveal more insight into COPD and other lung diseases.

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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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