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Age at menarche (AM) and age at natural menopause (ANM) are complex traits with a high heritability. Abnormal timing of menarche or menopause is associated with a reduced span of fertility and risk for several age-related diseases including breast, endometrial and ovarian cancer, cardiovascular disease, and osteoporosis. To identify novel genetic loci for AM or ANM in East Asian women and to replicate previously identified loci primarily in women of European ancestry by genome-wide association studies (GWASs), we conducted a two-stage GWAS. Stage I aimed to discover promising novel AM and ANM loci using GWAS data of 8073 women from Shanghai, China. The Stage II replication study used the data from another Chinese GWAS (n = 1230 for AM and n = 1458 for ANM), a Korean GWAS (n = 4215 for AM and n = 1739 for ANM), and de novo genotyping of 2877 additional Chinese women. Previous GWAS-identified loci for AM and ANM were also evaluated. We identified two suggestive menarcheal age loci tagged by rs79195475 at 10q21.3 (beta = −0.118 years, P = 3.4 × 10−6) and rs1023935 at 4p15.1 (beta = −0.145 years, P = 4.9 × 10−6) and one menopausal age locus tagged by rs3818134 at 22q12.2 (beta = −0.276 years, P = 8.8 × 10−6). These suggestive loci warrant a further validation in independent populations. Although limited by low statistical power, we replicated 19 of the 98 menarche loci and 5 of the 20 menopause loci previously identified in women of European ancestry in East Asian women, suggesting a shared genetic architecture for these two traits across populations.

To determine the dose–response of vitamin D3 supplementation on serum 25-hydroxyvitamin D [25(OH)D] among Chinese adults. In this 5-arm, randomized, double-blinded controlled trial, 76 healthy participants were assigned to orally administrate 0, 400, 800, 1200 or 2000 IU/d of vitamin D3 for 16 weeks. Serum 25(OH)D, parathyroid hormone, calcium, biomarkers of liver and renal function were measured at multiple time points. The mean (SD) serum 25(OH)D at baseline was 31.6 (8.7) nmol/L, and the dose–response relationship was curvilinear with a plateau around 6 weeks for all doses. At week 16, 25(OH)D was increased by 6.0 (6.5), 21.7 (15.8), 26.3 (12.6), 32.0 (12.8) and 36.3 (26.0) nmol/L for 0, 400, 800, 1200 and 2000 IU/d (all P ≤ 0.002), corresponding to approximately 19, 53, 67, 77 and 80 % of reversion of vitamin D deficiency, respectively. Daily intake of 800 IU vitamin D3 reached a targeted 25(OH)D ≥ 30 nmol/L in at least 97.5 % of Chinese, but not a targeted 25(OH)D ≥ 50 nmol/L even with 2000 IU/d. Change of 25(OH)D was inversely associated with change of PTH concentration (r = −0.39, P

Although microbiota-derived endotoxaemia has previously been shown to induce metabolic disorders, data from population-based longitudinal studies are scarce. This study therefore investigated the associations between lipopolysaccharide binding protein (LBP) levels and 6 year incident metabolic syndrome (MetS), as well as the potentially modifying effects of obesity status in middle-aged and older Chinese men and women. A total of 2,529 men and women aged 50–70 years from Beijing and Shanghai, China, were followed for 6 years. Those free of MetS at baseline (1,312) were included in the analyses for the risk of developing MetS. Baseline plasma LBP was measured using an ELISA kit. During the 6 year follow-up, 449 (34.2%) participants developed MetS. Baseline LBP was significantly associated with BMI, waist circumference, blood lipid profile and C-reactive protein (CRP) both at baseline and during follow-up (all p