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Birth weight variation is influenced by fetal and maternal genetic and non-genetic factors, and has been reproducibly associated with future cardio-metabolic health outcomes. In expanded genome-wide association analyses of own birth weight (n = 321,223) and offspring birth weight (n = 230,069 mothers), we identified 190 independent association signals (129 of which are novel). We used structural equation modeling to decompose the contributions of direct fetal and indirect maternal genetic effects, then applied Mendelian randomization to illuminate causal pathways. For example, both indirect maternal and direct fetal genetic effects drive the observational relationship between lower birth weight and higher later blood pressure: maternal blood pressure-raising alleles reduce offspring birth weight, but only direct fetal effects of these alleles, once inherited, increase later offspring blood pressure. Using maternal birth weight-lowering genotypes to proxy for an adverse intrauterine environment provided no evidence that it causally raises offspring blood pressure, indicating that the inverse birth weight-blood pressure association is attributable to genetic effects, and not to intrauterine programming.
Field-based sports require athletes to run sub-maximally over significant distances, often while contending with dynamic perturbations to preferred coordination patterns. The ability to adapt movement to maintain performance under such perturbations appears to be trainable through exposure to task variability, which encourages movement variability. The aim of the present study was to investigate the extent to which various wearable resistance loading magnitudes alter coordination and induce movement variability during running. To investigate this, 14 participants (three female and 11 male) performed 10 sub-maximal velocity shuttle runs with either no weight, 1%, 3%, or 5% of body weight attached to the lower limbs. Sagittal plane lower limb joint kinematics from one complete stride cycle in each run were assessed using functional data analysis techniques, both across the participant group and within-individuals. At the group-level, decreases in ankle plantarflexion following toe-off were evident in the 3% and 5% conditions, while increased knee flexion occurred during weight acceptance in the 5% condition compared with unloaded running. At the individual-level, between-run joint angle profiles varied, with six participants exhibiting increased joint angle variability in one or more loading conditions compared with unloaded running. Loading of 5% decreased between-run ankle joint variability among two individuals, likely in accordance with the need to manage increased system load or the novelty of the task. In terms of joint coordination, the most considerable alterations to coordination occurred in the 5% loading condition at the hip-knee joint pair, however, only a minority of participants exhibited this tendency. Coaches should prescribe wearable resistance individually to perturb preferred coordination patterns and encourage movement variability without loading to the extent that movement options become limited.