Although observational studies have explored factors that may be associated with osteoporosis, it is not clear whether they are causal. Osteoporosis in men is often underestimated. This study aimed to identify the causal risk factors associated with bone mineral density(BMD) in men. Single nucleotide polymorphisms (SNPs) associated with the exposures at the genome-wide significance (p < 5x10-8) level were obtained from corresponding genome-wide association studies (GWASs) and were utilized as instrumental variables. Summary-level statistical data for BMD were obtained from two large-scale UK Biobank GWASs. A Mendelian randomization (MR) analysis was performed to identify causal risk factors for BMD. Regarding the BMD of the heel bone, the odds of BMD increased per 1-SD increase of free testosterone (FT) (OR = 1.13, P = 9.4 × 10−17), together with estradiol (E2) (OR = 2.51, P = 2.3 × 10−4). The odds of BMD also increased with the lowering of sex-hormone binding globulin (SHBG) (OR = 0.87, P = 7.4 × 10−8) and total testosterone (TT) (OR = 0.96, P = 3.2 × 10−2) levels. Regarding the BMD of the lumbar spine, the odds of BMD increased per 1-SD increase in FT (OR = 1.18, P = 4.0 × 10−3). Regarding the BMD of the forearm bone, the odds of BMD increased with lowering SHBG (OR = 0.75, P = 3.0 × 10−3) and TT (OR = 0.85, P = 3.0 × 10−3) levels. Our MR study corroborated certain causal relationships and provided genetic evidence among sex hormone traits, lifestyle factors and BMD. Furthermore, it is a novel insight that TT was defined as a disadvantage for osteoporosis in male European populations.

BackgroundTelomere length shortening can cause senescence and apoptosis in various immune cells, resulting in immune destabilization and ageing of the organism. In this study, we aimed to systematically assess the causal relationship of leukocyte telomere length (LTL) with ankylosing spondylitis (AS) and rheumatoid arthritis (RA) using a Mendelian randomization study.MethodsLTL (n=472174) was obtained from the UK Biobank genome-wide association study pooled data. AS (n=229640), RA (n=212472) were obtained from FinnGen database. MR-Egger, inverse variance weighting, and weighted median methods were used to estimate the effects of causes. Cochran’s Q test, MR Egger intercept test, MR-PRESSO, leave-one-out analysis, and funnel plots were used to look at sensitivity, heterogeneity, and multiple effects. Forward MR analysis considered LTL as the exposure and AS, RA as the outcome. Reverse MR analysis considered AS, RA as the exposure and LTL as the outcome.ResultsIn the forward MR analysis, inverse variance-weighted and weighted median analysis results indicated that longer LTL might be associated with increased risk of AS (IVW: OR = 1.55, 95% CI: 1.14-2.11, p = 0.006). MR Egger regression analysis showed no pleiotropy between instrumental variables (IVs) (Egger intercept= 0.008, p = 0.294). The leave-one-out analysis showed that each single nucleotide polymorphism (SNP) of AS was robust to each outcome. No significant causal effects were found between AS, RA and LTL in the reverse MR analysis.ConclusionLonger LTL may be related with an increased risk of developing AS, and these findings provide a foundation for future clinical research on the causal association between LTL and AS.