2). There was evidence for an association between the C allele of rs9594759 and slower chair rise times (p = 0.04). There was evidence for an association between the C allele of rs9594759 and poorer standing balance (p = 0.04), although this effect was only seen in females with some evidence for a sex difference (p = 0.05 for heterogeneity between males and females, Fig.

S2). There was evidence for heterogeneity between males and females for the association between rs3815148 (COG5) and standing balance, (p = 0.012, Fig. Fulvestrant chemical structure S3) with the observed effects in opposite directions. No other genotypic associations with physical capability measures or evidence for sex differences were observed. Additional adjustment for alcohol consumption for the genotypic effects of rs9594759 did not substantially affect its associations with chair rises (pooled beta for z-score = − 0.031, 95% CI: − 0.060 to − 0.002, p = 0.04, n = 8184) and standing balance in females IDH inhibitor clinical trial (pooled OR = 0.85, 95% CI: 0.75–0.96, p = 0.01, data not shown). In only a relatively small number of tests did the full genotype model represent a significantly better fit than the per allele model: rs9594759 for weight and BMI in Boyd Orr, smoking

status and timed walk in LBC1921; rs2941740 for smoking status in ELSA, socio-economic position in NSHD and balance in CaPS. In this large, multi-cohort study of older adults we investigated associations between robust genetic markers of serum calcium, bone mineral density and osteoarthritis risk and measures of physical capability in six UK cohorts of 12,836 adults aged between 52 and 90 + years. We found marginal evidence for an association between rs1801725 (CASR) and grip strength, with carriers of the allele

associated with raised serum calcium Amobarbital levels, identified from GWAS [19] and [20], having lower grip strength. However, the effect size was small at − 0.03 z-score units for carriers of the T allele, adjusting for age and sex, representing 0.33 kg assuming a standard deviation of 11. We also found some evidence for the association of the BMD-raising allele (C) of rs9594759 (RANKL) [32], [33] and [34] with slower chair rise times and poorer standing balance. This direction was unexpected; however, the interpretation of these results should be treated with caution as the HWE condition was not met for rs9594759 (RANKL) in NSHD and CaPS, and whilst exclusion of the studies is not recommended [59], both studies contributed to the meta-analysis for standing balance and NSHD also contributed to that for chair rises. There were no observed associations with the physical capability measures for the BMD-raising allele of rs2941740 (ESR1).