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New gene locations impact heart rate and life expectancy

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02 November 2016

​In a large-scale genome-wide association study among more than 134,000 participants, UMCG researchers led by cardiologist Pim van der Harst have identified 64 gene locations that appear to be related to our heart rate. Forty-six of these locations had not previously been associated with heart frequency. The study also suggests that a 5-beat per minute increase in heart rate leads to a reduced life expectancy of 2.9 years for men and 2.6 years for women. Van der Harst is publishing his findings in the renowned scientific magazine Nature Genetics.

Heart rate is a feature that can be influenced by various environmental factors and various circumstances such as exertion, stress and disease. We know a lot about the various environmental factors that affect heart rate, but very little about which genes play a role in this context. The objective of Van der Harst’s study was to discover new genes (and gene locations) in order to better understand the biology and regulation of heart rate and its relation to life expectancy and healthy ageing.

Resting heart rate correlates with life expectancy. This connection is very clear in the animal world. Large animals such as elephants or whales have a slow heart rate (15-30 beats per minute) and live 20 to 30 years. Small animals such as mice or hamsters have a high heart rate (400-600 beats per minute) and live 1 to 3 years. This might be due to the fact that the heart has to burn more energy and use more oxygen to beat faster. This underlying metabolism, including the accompanying oxidative stress, plays an important role in ultimately determining life expectancy. Among people too, a link has been found between the measured resting heart rate and survival. People with a higher resting heart rate have an increased risk of suffering from a heart attack or sudden death.

The researchers conducted a genome-wide association study, meaning that they investigated the entire human genome structure. For this study, they used data collected of heart rate from  134,251 people participating in the UK Biobank initiative and investigated its relationship to nearly 20 million markers on the genome. They subsequently re-investigated and confirmed the observed links in 130,795 additional people from 4 other cohorts. They identified a total of 64 gene locations that are linked to resting heart rate, 46 of which had not previously been linked to heart rate. 

In his study Van der Harst established a link between genetic variations that influence heart rate and mortality. The study shows that the risk of death increases by 20% with an increase in heart rate of 5 beats per minute. “It is even more interesting to look at life-expectancy”, co-investigator Ruben Eppinga said, “this study also suggested that an increase in heart rate of 5 beats per minute reduces life expectancy by 2.9 years in men and 2.6 years in women”. According to Van der Harst, this effect can be explained in one of at least two ways: It may be that the genetic variations directly impact the increased risk of mortality via the heart rate, or it may be that the genes impact the underlying biological processes. Van der Harst warns for over interpretation of the data, “we did not study whether lowering the heart rate, for example by lifestyle improvements or medicines, will translate into increased life-expectancy. It is certainly an interesting thought but we should be careful to draw conclusions based on the current data”. The researchers were able to conduct this study thanks to data from sources such as the LifeLines, UK Biobank, 23andME and DECODE databases. LifeLines is a large-scale health study that monitors the health of 167,000 inhabitants of the northern Netherlands over a period of 30 years.