SNPwatch: Researchers Identify Genetic Variants Linked To Heart Rhythm And Possibly Sudden Cardiac Death

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.

Each beat of your heart is the result of a highly coordinated electrical system.  An impulse that starts in a few tiny cells spreads throughout the whole organ, causing cardiac cells to contract, pumping your blood in the never-ending circuit that courses through your body.

The “QT interval”, a measurement made from electrocardiogram recordings of the heart’s electrical activity, reflects the amount of time it takes for cells to reset after a contraction.  If this interval is abnormally long or short, it can scramble the electrical system of the heart, causing an erratic beat and limiting the heart’s ability to supply the body with enough newly oxygenated blood.  This can lead to fainting and, in some cases, sudden cardiac death.

Several genetic mutations that cause long and short QT intervals are known to run in families.  But these mutations don’t account for all cases of sudden cardiac death, nor do they explain the normal variation in QT interval seen in the population.  To learn more about the genetics of heartbeat regulation, two independent research teams (QTGEN and QTSCD) looked for genetic variants associated with natural variation in QT interval in more than 28,000 people.  The results, published online yesterday in the journal Nature Genetics, identify a total of 14 SNPs that can now be used as the basis of future research aimed at understanding susceptibility to QT interval-related irregular heart beat and sudden cardiac death.

“The reason people die from this cardiovascular disorder is because we know nothing about the antecedents,” said Aravinda Chakravarti, QTSCD study senior investigator, in a statement.  “It’s like a truck barreling down a slope: there’s no way to stop it.  The only way out is to understand the science of this in a deep, meaningful way.  If we know, we can begin to intervene.”

More than half of the variants identified by the researchers are located in genes already known to be involved in heart cell regulation, some of which are also mutated in familial syndromes characterized by long QT intervals.  But five of the SNPs are in genes not previously recognized as players in the electrical activity of the heart.  These findings open up new avenues for cardiovascular research.

According to the authors of one study (QTGEN), the variants found in these studies together explain more of the variation in QT interval seen in the population than any other factor except for heart rate.  But they warn that more research is still needed to determine whether the variants actually contribute to the risk for sudden cardiac death in addition to lengthening QT intervals.

The following table lists the variations reported in the studies discussed above.  SNPs available to 23andMe customers are linked to the Browse Raw Data feature.  Note that the individual changes in QT interval attributable to each individual SNP are very small compared to the normal range of 300 to 450 milliseconds (ms). THESE SNPS CANNOT BE USED TO DIAGNOSE OR PREDICT LONG OR SHORT QT SYNDROME.

SNP Version Change in QT Interval (ms) Notes
rs12143842 T +3.15
rs12029454 A +2.975
rs16857031 G +2.625
rs2074238 T -7.875
rs37062 G -1.75
rs11756438 A +1.4
rs12576239 T +1.75
rs846111 C +1.75
rs4725982 T +1.575
rs8049607 T +1.225
rs1805128 T +0.875 Not supported in QTSCD study
rs12053903 C -1.225
rs1052536 T -1.05 This SNP is a proxy for rs2074518, which was reported in the QTGEN study
rs2968864 C -1.4