Genome-wide association study of self-reported walking pace suggests beneficial effects of brisk walking on health and survival

Abstract

Walking is a simple form of exercise, widely promoted for its health benefits. Self-reported walking pace has been associated with a range of cardiorespiratory and cancer outcomes, and is a strong predictor of mortality. Here we perform a genome-wide association study of self-reported walking pace in 450,967 European ancestry UK Biobank participants. We identify 70 independent associated loci (P < 5 × 10−8), 11 of which are novel. We estimate the SNP-based heritability as 13.2% (s.e. = 0.21%), reducing to 8.9% (s.e. = 0.17%) with adjustment for body mass index. Significant genetic correlations are observed with cardiometabolic, respiratory and psychiatric traits, educational attainment and all-cause mortality. Mendelian randomization analyses suggest 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 self-reported walking pace is a pragmatic target for interventions aiming for general benefits on health.

Linking objective measures of physical activity and capability with brain structure in healthy community dwelling older adults

“…Further, follow-up Mendelian randomization analyses, which allows for causal inference, suggested that increasing walking pace decreases cardiometabolic risk, in line with current public health advice (Timmins et al, 2020). Moreover, a number of studies have reported that walking speed is a strong predictor of mortality (Cooper et al, 2010; Ganna & Ingelsson, 2015) and a relevant index of “vital aging” (Vermeulen et al, 2011).…”

Linking objective measures of physical activity and capability with brain structure in healthy community dwelling older adults

“…Approximately 10% of the variance in self-reported walking speed was attributed to individual differences in common genetic variants, and significant genetic correlations were reported between self-reported walking speed and cardiometabolic, respiratory and psychiatric traits, educational attainment and mortality. Further, follow-up Mendelian randomization analyses, which allows for causal inference, suggested that increasing walking pace decreases cardiometabolic risk, in line with current public health advice ( Timmins et al, 2020 ). Moreover, a number of studies have reported that walking speed is a strong predictor of mortality ( Cooper et al, 2010 , Ganna and Ingelsson, 2015 ) and a relevant index of “vital aging” ( Vermeulen et al, 2011 ).…”

Causal Associations of Self-Reported Walking Pace with Telomere Length in 405,981 middle-aged adults: a UK Biobank study

“…We matched variants to the publicly available walking pace GWAS data that were unadjusted and adjusted for BMI, matching 121 variants. For walking pace on LTL (part 2) we considered 70 genome-wide significant (P<5.0x10 -8 ) independent genetic variants as the instrument from the unadjusted GWAS using weights from both the unadjusted GWAS and the BMI-adjusted GWAS [15]. These were matched to the LTL GWAS [18], matching all variants.…”

“…Similarly, accelerometer-assessed measures of PA in UK Biobank suggest that as little as 10 min of brisk walking a day is associated with longer life expectancy [14]. A genome-wide association study (GWAS) on self-reported walking pace within UK Biobank identified 70 independent SNPs at genome-wide significance [15], close to an order of magnitude greater than the number reported for other self-reported or accelerometer-assessed measures of PA traits within the same cohort [16].…”

“…The importance of walking pace as a marker and potential promoter of health is likely to reflect it being a complex functional activity influenced by many factors, such as motor control, musculoskeletal health, cardiorespiratory fitness and lung capacity, habitual activity levels, cognition, motivation, and mental health [3,13,15]. These factors also align to the concept of biological age, which relates to an individual's ability to maintain a robust homeostasis when subject to stressors [17].…”