Obesity, birth weight and lifestyle factors have been found associated with the risk of frailty in observational studies, but whether these associations are causal is uncertain. We conducted a two-sample Mendelian randomization study to investigate the associations. Genetic instruments associated with the exposures at the genome-wide significance level (p < 5 × 10-8) were selected from corresponding genome-wide association studies (n = 143,677 to 703,901 individuals). Summary-level data for the frailty index were obtained from the UK Biobank (n = 164,610) and Swedish TwinGene (n = 10,616). The β of the frailty index was 0.15 (p = 3.88 × 10-9) for 1 standard deviation increase in the prevalence of smoking initiation, 0.19 (p = 3.54 × 10-15) for leisure screen time, 0.13 (p = 5.26 × 10-7) for body mass index and 0.13 (p = 1.80 × 10-4) for waist circumference. There was a suggestive association between genetically predicted higher birth weight and moderate-to-vigorous intensity physical activity with the decreased risk of the frailty index. We observed no causal association between genetically predicted age of smoking initiation and alcoholic drinks per week with the frailty index. This study supports the causal roles of smoking initiation, leisure screen time, overall obesity, and abdominal obesity in frailty. The possible association between higher birth weight, proper physical activity and a decreased risk of frailty needs further confirmation.
Keywords: Mendelian randomization; frailty; lifestyle factors; obesity.