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Both bone mineral density (BMD) and lean body mass (LBM) are important physiological measures with strong genetic determination. Besides, BMD and LBM might have common genetic factors. Aiming to identify pleiotropic genomic loci underlying BMD and LBM, we performed bivariate genome-wide association study meta-analyses of femoral neck bone mineral density and LBM at arms and legs, and replicated in the large-scale UK Biobank cohort sample. Combining the results from discovery meta-analysis and replication sample, we identified three genomic loci at the genome-wide significance level (p < 5.0 × 10–8): 2p23.2 (lead SNP rs4477866, discovery p = 3.47 × 10–8, replication p = 1.03 × 10–4), 16q12.2 (rs1421085, discovery p = 2.04 × 10–9, replication p = 6.47 × 10–14) and 18q21.32 (rs11152213, discovery p = 3.47 × 10–8, replication p = 6.69 × 10–6). Our findings not only provide useful insights into lean mass and bone mass development, but also enhance our understanding of the potential genetic correlation between BMD and LBM. [ABSTRACT FROM AUTHOR]

Aiming to uncover a shared genetic basis of abdominal obesity and osteoporosis, we performed a bivariate GWAS meta-analysis of femoral neck BMD (FNK-BMD) and trunk fat mass adjusted by trunk lean mass (TFMadj) in 11,496 subjects from 6 samples, followed by in silico replication in the large-scale UK Biobank (UKB) cohort. A series of functional investigations were conducted on the identified variants. Bivariate GWAS meta-analysis identified two novel pleiotropic loci 12q15 (lead SNP rs73134637, p = 3.45 × 10–7) and 10p14 (lead SNP rs2892347, p = 2.63 × 10–7) that were suggestively associated and that were replicated in the analyses of related traits in the UKB sample (osteoporosis p = 0.06 and 0.02, BMI p = 0.03 and 4.61 × 10–3, N up to 499,520). Cis-eQTL analysis demonstrated that allele C at rs73134637 was positively associated with IFNG expression in whole blood (N = 369, p = 0.04), and allele A at rs11254759 (10p14, p = 9.49 × 10–7) was negatively associated with PRKCQ expression in visceral adipose tissue (N = 313, p = 0.04) and in lymphocytes (N = 117, p = 0.03). As a proof-of-principle experiment, the function of rs11254759, which is 235 kb 5′-upstream from PRKCQ gene, was investigated by the dual-luciferase reporter assay, which clearly showed that the haplotype carrying rs11254759 regulated PRKCQ expression by upregulating PRKCQ promoter activity (p = 4.60 × 10–7) in an allelic specific manner. Mouse model analysis showed that heterozygous PRKCQ deficient mice presented decreased fat mass compared to wild-type control mice (p = 3.30 × 10–3). Mendelian randomization analysis demonstrated that both FNK-BMD and TFMadj were causally associated with fracture risk (p = 1.26 × 10–23 and 1.18 × 10–11). Our findings may provide useful insights into the genetic association between osteoporosis and abdominal obesity. [ABSTRACT FROM AUTHOR]

• The study the significant mixture effect between LPA, MPA, and VPA on the risk of dementia. • Taking into account genetic risk, physical activity patterns that are more adherent to MPA and VPA are associated with a reduced risk of dementia. • The findings reveal that the effectiveness of specific types of physical activity in reducing the risk of dementia varies based on the subtype of dementia. MPA is found to be more effective for Alzheimer's disease, while VPA is more powerful for vascular dementia. There is limited information on the mixture effect and weights of light physical activity (LPA), moderate physical activity (MPA), and vigorous physical activity (VPA) on dementia risk. A prospective cohort study was conducted based on the UK Biobank dataset. We included participants aged at least 45 years old without dementia at baseline between 2006-2010. The weighted quantile sum regression was used to explore the mixture effect and weights of three types of physical activity on dementia risk. This study includes 354,123 participants, with a mean baseline age of 58.0-year-old and 52.4 % of female participants. During a median follow-up time of 12.5 years, 5,136 cases of dementia were observed. The mixture effect of LPA, MPA, and VPA on dementia was statistically significant (β: -0.0924, 95 % Confidence Interval (CI): (-0.1402, -0.0446), P < 0.001), with VPA (weight: 0.7922) contributing most to a lower dementia risk, followed by MPA (0.1939). For Alzheimer's disease, MPA contributed the most (0.8555); for vascular dementia, VPA contributed the most (0.6271). For Alzheimer's disease, MPA was identified as the most influential factor, while VPA stood out as the most impactful for vascular dementia. [ABSTRACT FROM AUTHOR]

Background: Fat mass and lean mass are two biggest components of body mass. Both fat mass and lean mass are under strong genetic determinants and are correlated., Methods: We performed a bivariate genome-wide association meta-analysis of (lean adjusted) leg fat mass and (fat adjusted) leg lean mass in 12,517 subjects from 6 samples, and followed by in silico replication in large-scale UK biobank cohort sample (N = 370 097)., Results: We identified four loci that were significant at the genome-wide significance (GWS, α = 5.0 × 10 -8 ) level at the discovery meta-analysis, and successfully replicated in the replication sample: 2q36.3 (rs1024137, p discovery  = 3.32 × 10 -8 , p replication  = 4.07 × 10 -13 ), 5q13.1 (rs4976033, p discovery  = 1.93 × 10 -9 , p replication  = 6.35 × 10 -7 ), 12q24.31 (rs4765528, p discovery  = 7.19 × 10 -12 , p replication  = 1.88 × 10 -11 ) and 18q21.32 (rs371326986, p discovery  = 9.04 × 10 -9 , p replication  = 2.35 × 10 -95 ). The above four pleiotropic loci may play a pleiotropic role for fat mass and lean mass development., Conclusions: Our findings further enhance the understanding of the genetic association between fat mass and lean mass and provide a new theoretical basis for their understanding.