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Background: Grip strength is a well-established predictor of various chronic conditions and all-cause mortality. Body weight and physical activity (PA) are considered potential determinants of muscle strength. This study aimed to investigate gender-specific associations of baseline obesity and physical inactivity with long-term changes in grip strength among middle-aged and older European adults., Methods: Data from the Survey of Health, Ageing and Retirement in Europe 2004-2015 which was conducted in 12 countries were analysed. Grip strength was repeatedly measured at five follow-up visits with average 2-year intervals. Obesity and physical inactivity at baseline were primary exposures. Generalised estimated equations stratified by gender were fitted., Results: This study included 8616 males and 10 088 females with a median follow-up of 9.42 years. Significant interactions between obesity and time with grip strength were identified in both males (χ 2 interaction =16.65, p = 0.002) and females (χ 2 interaction =10.80, p = 0.029). No significant interaction between physical inactivity and time with grip strength was identified in males (χ 2 interaction =9.42, p = 0.051) or females (χ 2 interaction =5.62, p = 0.230). Those who were less physically active at baseline had weaker grip strength from the beginning at baseline (β = -2.753, p < 0.001 for males and β = -1.529, p < 0.001 for females) to Visit 6 (β = -2.794, p < 0.001 for males and β = -1.550, p < 0.001 for females). Further combined analysis suggested a trend that exposure to both obesity and physical inactivity was related to the fastest decline rate of grip strength., Conclusions: This study provides the additional evidence that PA and obesity prevention earlier in life play an important role in maintaining grip strength during ageing., Competing Interests: Competing interests: None declared., (© Author(s) (or their employer(s)) 2019. No commercial re-use. See rights and permissions. Published by BMJ.)

Platelets are the second most abundant cell type in blood and are essential for maintaining haemostasis. Their count and volume are tightly controlled within narrow physiological ranges, but there is only limited understanding of the molecular processes controlling both traits. Here we carried out a high-powered meta-analysis of genome-wide association studies (GWAS) in up to 66,867 individuals of European ancestry, followed by extensive biological and functional assessment. We identified 68 genomic loci reliably associated with platelet count and volume mapping to established and putative novel regulators of megakaryopoiesis and platelet formation. These genes show megakaryocyte-specific gene expression patterns and extensive network connectivity. Using gene silencing in Danio rerio and Drosophila melanogaster, we identified 11 of the genes as novel regulators of blood cell formation. Taken together, our findings advance understanding of novel gene functions controlling fate-determining events during megakaryopoiesis and platelet formation, providing a new example of successful translation of GWAS to function.