Using Mendelian randomisation (MR) we find evidence in favour of causal relationships between self-reported walking pace and several traits associated with mortality. Through these analyses we identify 70 genetic loci for self-reported walking pace and show that this trait shares its genetic architecture with other cardiometabolic risk factors, including educational attainment and cognitive outcomes. We aimed to identify associated genetic variants and their possible function, quantify the genetic correlation of walking pace with other complex traits, and assess the potential of self-reported walking pace as a modifiable health-related exposure. Participants self-reported their walking pace as вЂњslowвЂќ, вЂњsteady/averageвЂќ or вЂњbriskвЂќ. To examine the genetic component of self-reported walking pace, we performed a genome-wide association study (GWAS) in UK Biobank, a prospective study of approximately 450,000 adults of European descent, in addition to approximately 50,000 participants of other ethnicities, aged between 40 and 69 years at baseline 9. Genome-wide significant markers of objectively measured gait speed were not identified in these studies, which had a maximum sample size of 31,479. These studies focussed on older adults, giving insight into the biological mechanisms underlying age-related diseases and physical mobility 7, 8. To date, studies examining the genetic component of walking pace have analysed objectively measured gait speed, where speed is assessed by timing participants to walk a distance of up to 8вЂ‰m. These questions can be addressed with knowledge of the genetics of walking pace. Most notably, self-reported habitual walking pace has been identified as one of the strongest predictors of all-cause mortality 4, even when adjusting for the effects of established risk factors such as body mass index (BMI) 5 and other lifestyle behaviours including smoking 6.Дespite the strong associations of self-reported walking pace with health and survival, it is unclear whether these associations arise from common biological processes, including genetic predisposition, nor whether there are causal effects of walking pace on health outcomes. However, recent studies have observed a brisk habitual walking pace, self-reported through questionnaire or verbal interview, to be associated with reduced risk of a range of cardiorespiratory and cancer outcomes 2, 3. The public health recommendations for walking focus particularly on increasing the time spent walking and the number of steps walked, with walking at a faster pace receiving less emphasis 2. Walking is a simple and convenient form of exercise that is widely promoted for its benefit to physical fitness and overall health 1. Given its low heritability and simple measurement, these findings suggest that self-reported walking pace is a pragmatic target for interventions aiming for general benefits on health. Mendelian randomization analyses suggest a potential causal link of increasing walking pace with a lower cardiometabolic risk profile. Significant genetic correlations are observed with cardiometabolic, respiratory and psychiatric traits, educational attainment and all-cause mortality. We estimate the SNP-based heritability as 13.2% (s.e.вЂ‰=вЂ‰0.21%), reducing to 8.9% (s.e.вЂ‰=вЂ‰0.17%) with adjustment for body mass index.

We identify 70 independent associated loci ( PвЂ‰<вЂ‰5вЂ‰Г—вЂ‰10 в€’8), 11 of which are novel. Here we perform a genome-wide association study of self-reported walking pace in 450,967 European ancestry UK Biobank participants. Self-reported walking pace has been associated with a range of cardiorespiratory and cancer outcomes, and is a strong predictor of mortality. Walking is a simple form of exercise, widely promoted for its health benefits.

Brisk walking definition