SNPwatch: Study Finds Genetic Links to Brain Aneurysm in Both Japanese and European Populations

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.

Experts estimate that 5% of the United States population — at least 15 million people — have weak spots in the arteries of their brains known as aneurysms. Each year about 27,000 of these bulging arteries burst, releasing blood into the space around the brain and potentially leading to stroke, brain damage or death.

The siblings of people who have had a ruptured brain aneurysm are four times more likely to suffer the same fate, suggesting that genes play a part in determining risk. So far, however, studies of families with a history of brain aneurysm and genes thought to be likely candidates have failed to produce any convincing genetic links.

A new study published online yesterday in Nature Genetics reports three genetic variants that, when combined, can increase the odds of brain aneurysm by almost three-fold. The variants increased risk independent of sex, family history and age.

Kaya Bilguvar and colleagues began by screening hundreds of thousands of SNPs in two European samples, one from Finland and one from the Netherlands. They then looked for evidence that the most strongly associated SNPs also increased the likelihood of aneurysm in a Japanese sample. All told, more than 2,100 people with brain aneurysm and 8,000 controls were studied. The authors say that they used a diverse population for their studies so that the results could be extended to a broader segment of the world’s population.

The researchers found associations between SNPs on chromosome 2, 8 and 9 (rs700651, rs10958409 and rs1333040, respectively) and brain aneurysm risk. A person with five or six “risky” copies (there are six possible – everyone has two copies of each of the three SNPs) has almost three times greater odds of having a brain aneurysm compared to someone who has zero or only one risky copy.

(23andMe customers can check their data for these SNPs using the Browse Raw data feature. A table with all of the relevant information is provided at the end of this post.)

SNPs in the same region of chromosome 9 as rs1333040 have previously been associated with arterial diseases, including brain aneurysm.

In many cases the first sign of a brain aneurysm is the catastrophic bleeding in the brain that happens when it ruptures. The authors of the current report caution that further work will be needed in this area and that there are most likely more DNA variants to be found. But they say their findings, in combination with assessment of other risk factors, could help identify people with brain aneurysms before it’s too late.

SNP Chromosome Risk Version Effect of 1 Copy Effect of 2 Copies
rs700651 2 G 1.18 1.56
rs10958409 8 A 1.37 1.79
rs1333040 9 T 1.29 1.67

“Effect” is the increase in odds compared to someone with two copies of the non-risk version of each SNP as calculated in Bilguvar et al for the combined Finnish, Dutch and Japanese sample.


  • Hellman

    This is really interesting, considering how devastating an aneurysm can be. I have two questions.

    1) If doctors do identify people with increased risk of aneurysm, what is the treatment? Doses of blood thinners?

    2) The authors say that brain aneurysm likelihood is increased three-fold. How is that risk calculated based on the table you show? Are the risk effects simply additive?

    Thanks for the info!

    AH

  • http://www.23andme.com ErinC

    Hi AH,

    From the National Heart Lung and Blood Institute:

    (http://www.nhlbi.nih.gov/health/dci/Diseases/arm/arm_treatments.html)

    “Goals of Treatment

    Some aneurysms, mainly small ones that are not causing pain, can be treated with “watchful waiting.” Others need to be treated to prevent growth and complications. The goals of treatment are to prevent the aneurysm from growing, prevent or reverse damage to other body structures, prevent or treat a rupture, and to allow you to continue to participate in normal daily activities.

    Treatment Options

    Medicine and surgery are the two types of treatment for an aneurysm. Medicines may be prescribed before surgery or instead of surgery. Medicines are used to reduce pressure, relax blood vessels, and reduce the risk of rupture. Beta blockers and calcium channel blockers are the medicines most commonly used.

    Surgery may be recommended if an aneurysm is large and likely to rupture.”

    As for your second question:

    Odds ratios are generally assumed to be multiplicative. Using the table I show in the post, you would get an OR of about 4.7 if you multiplied the effect of having two risk copies at each SNP.

    So why does it only say three-fold in the paper?

    It was a conservative estimate by the authors that takes into account the variability between the different populations and the rarity of actually having this many risk copies.

    Probably the most important thing to take away from this story is that the researchers found some SNPs that might eventually help them understand more about brain aneurysms and/or help predict who is at risk.

  • nick

    Very interesting indeed. Keep the SNPwatch posts coming. You introduce a lot of articles I wouldn’t otherwise come across in my research.

    Nick

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