Genetic epidemiology of self-reported walking pace

Walking is a simple and convenient form of exercise that is widely promoted in guidelines for its benefit to physical fitness and overall health. Many prospective epidemiological studies have recorded walking activity through questionnaire items, consistently observing that increased habitual walking pace is associated with marked risk reductions in cardiovascular disease and all-cause mortality. Despite this, 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.

To address these questions, I have examined the relationship between walking pace, health and survival using comprehensive genetic and phenotypic data from UK Biobank, applying a range of new methods in genetic epidemiology.

I performed a genome-wide association study of walking pace in a large European ancestry cohort, identifying 70 independent associated loci (P < 5 × 10−8), 11 of which are novel. Annotations of the top hits suggested a strong contribution of pleiotropy to self-reported walking pace, implicating a range of cardiometabolic and neurocognitive pathways.

I estimated the SNP-heritability as 13.2% (s.e. = 0.21%), reducing to 8.9% (s.e. = 0.17%) with adjustment for body mass index, suggesting that walking pace has only a modest genetic contribution. Significant genetic correlations were observed between walking pace and objective physical activity accelerometer metrics, alongside cardiometabolic, respiratory and psychiatric traits, educational attainment, and all-cause mortality. Cross-population genetic correlations suggested limited transferability of genetic findings to non-European populations.Finally, Mendelian randomisation analyses suggested a potential causal link of increasing walking pace with a lower cardiometabolic risk profile. Given its low heritability and simple measurement, these findings suggest that walking pace is a pragmatic target for interventions aiming for general benefits on health.