Background Vitamin D deficiency has been associated with type 2 diabetes (T2D) and metabolic syndrome (MS) and its components. However, it is unclear whether a low concentration of vitamin D is the cause or consequence of these health conditions. Thus, this study aimed to evaluate the association of vitamin D concentrations and its genetic risk scores (GRSs) with MS and its component diseases, such as T2D, in middle-aged and elderly participants from rural eastern China. Methods A subset of 2393 middle-aged and elderly individuals were selected from 70,458 participants of the Nantong Chronic Diseases Study of 2017–2018 in China. We used two 25-hydroxyvitamin D (25[OH]D) synthesis single-nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657) and two 25(OH) D metabolism SNPs (GC-rs2282679 and CYP24A1-rs6013897) for creating GRSs, which were used as instrumental variables to assess the effect of genetically lowered 25(OH) D concentrations on MS and T2D based on the Wald ratio. F statistics were used to validate that the four SNPs genetically determined 25(OH) D concentrations. Results Compared to vitamin D sufficient individuals, individuals with vitamin D insufficiency had an odds ratio (OR [95% confidence interval {CI}]) of MS of 1.30 (1.06–1.61) and of T2D of 1.32 (1.08–1.64), individuals with vitamin D deficiency had an ORs (95% CI) of MS of 1.50 (1.24–1.79) and of T2D of 1.47 (1.12–1.80), and those with vitamin D severe deficiency had an ORs (95% CI) of MS of 1.52 (1.29–1.85) and of T2D of 1.54 (1.27–1.85). Mendelian randomization analysis showed a 25-nmol/L decrease in genetically instrumented serum 25(OH) D concentrations using the two synthesis SNPs (DHCR7 and CYP2R1 genes) associated with the risk of T2D and abnormal diastolic blood pressure (DBP) with ORs of 1.10 (95%CI: 1.02–1.45) for T2D and 1.14 (95%CI: 1.03–1.43) for DBP. Conclusions This one sample Mendelian randomization analysis shows genetic evidence for a causal role of lower 25(OH) D concentrations in promoting of T2D and abnormal DBP in middle-aged and elderly participants from rural China.

Background: We explored the association between several chronic diseases and depressive symptoms (DSs) at individual and couple levels.Methods: Data were derived from the 2018 China Health and Retirement Longitudinal Study, including 5365 middle-aged and elderly couples. DSs were measured using the 10-item Center for Epidemiological Studies Depression Scale, and chronic diseases were determined by self-report and doctor diagnosis. Multivariate logistic regression models were used to estimate the association between chronic diseases and DSs.Results: Couples’ unilaterality with different numbers of chronic diseases had increased 16%–289% risk on their own DSs and 24%–39% risk on spousal DSs. Couples with different numbers of chronic diseases increased their co-depression by 183%–834%, which was mainly increased in wives’ depressive symptoms (WDSs) by 51%–301%, more severe than husbands’ depressive symptoms (HDSs). WDSs and HDSs increased by 13%–111% in couples with unilateral respiratory disease, dyslipidaemia, digestive disease, arthritis, kidney disease, stroke, memory-related disease and by 24%–244% in couples’ co-morbidity of respiratory, metabolic, and digestive diseases, arthritis, heart problem, kidney disease, stroke. Further, co-depression increased by 34%–458% in couples with unilaterality/co-morbidity of these chronic diseases.Conclusions: Couples’ unilaterality/co-morbidity of most chronic diseases were associated with WDSs, HDSs, and co-depression. WDSs were more susceptible to chronic diseases than HDSs. Physical health of an individual could predict not only his/her own mental health but also his/her spouse’s mental health.

Background: Vitamin D deficiency is common around the world, but the association between vitamin D deficiency with metabolic syndrome and its associated diseases is unclear.Methods: A subset of 2393 participants from the Nantong Chronic Diseases Study (NCDS) of 2017-2018 were included in this study.The risk of MS and its associated diseases from low vitamin D levels were assessed by genetic scores using two 25(OH)D synthesis single nucleotide polymorphisms (SNPs) (DHCR7-rs12785878 and CYP2R1-rs10741657), one transport SNP (GC-rs2282679) and one catabolism SNP (CYP24A1-rs6013897).Results: Odds Ratios (ORs) for decreased risk of MS and type 2 diabetes (T2D) was 0.73 and 0.79 in the deficient, 0.53 and 0.67 in the insufficient, and 0.54 and 0.60 in the sufficient categories of serum vitamin D levels, respectively. Mendelian randomization analysis showed per 25nmol/L higher genetically instrumented serum 25(OH)D concentration using the two synthesis SNPs: DHCR7+CYP2R1 genes, associated with a 7% lower risk of T2D. The highest tertile vs the lowest tertile of genetic scores using the three SNPs of DHCR7+CYP2R1+GC genes showed a 10% lower risk of T2D. Also, the group with higher genetic scores among these two and three SNPs were both associated with lower risk of abnormal diastolic blood pressure (DBP) (P=0.0162 and 0.0045 respectively).Conclusions: Our Mendelian randomization analysis showed no genetic evidence for a causal role of lower vitamin D level in the development of MS, but showed a causal role in the development of T2D and DBP in middle-aged and elderly participants from rural China.