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An association between vitamin D deficiency and hypertension has been observed in numerous studies. However, blood pressure improvements resulting from supplementation with vitamin D have been inconsistent. The causal relationship between vitamin D deficiency and hypertension is still unclear and was investigated in this family-based study. A total of 1370 individuals from both vitamin D deficiency and hypertension families were included. First, the heritability of vitamin D deficiency was estimated by the Falconer method. Second, SNPs (single nucleotide polymorphisms) of vitamin D metabolic and functional pathway genes associated with vitamin D deficiency were screened by a family-based association test, and the findings were further verified in nuclear families with vitamin D deficiency. Finally, a family-based association test was applied to investigate the association between selected SNPs associated with vitamin D deficiency and hypertension. The heritability of vitamin D deficiency was 50.4% in this family-based study. Allele C of rs3847987 was a risk factor for vitamin D deficiency (OR: 1.639, 95% CI: 1.170-2.297, P = 0.004). Furthermore, a family-based association of rs3847987 with hypertension was found in both additive and recessive models (P < 0.05). In addition, vitamin D deficiency was associated with hypertension (OR: 1.317, 95% CI: 1.022-1.698, P = 0.033). In conclusion, rs3847987 in the VDR gene was associated with both vitamin D deficiency and hypertension. Therefore, vitamin D deficiency may be a causal factor for hypertension., (© 2022. The Author(s), under exclusive licence to The Japanese Society of Hypertension.)

Objectives: Vitamin D deficiency was associated with obesity. However, the causal relationship remains controversial. We hypothesized that there would be family-based associations in both vitamin D deficient families and obese families for the SNPs associated with vitamin D deficiency, if vitamin D deficiency was a causal factor of obesity. We aimed to investigate the family-based association of SNPs in CYP27B1 with both vitamin D deficiency and obesity., Methods: Four hundred and nineteen pedigrees containing 1505 rural individuals aged from 18 to 79 years in Henan Province of China were included in this study. Family-based associations of rs10877012 and rs4646536 in CYP27B1 with vitamin D deficiency and obesity were investigated. Serum 25(OH)D3 concentration <20 μg/L was defined as vitamin D deficiency. BMI ≥ 28 kg/m 2 was applied for obesity definition. Taqman assays were applied for SNP genotyping. Family-based associations were investigated with FBAT software., Results: It was shown that vitamin D deficiency was a risk factor of obesity (adjusted OR: 1.332, 95% CI: 1.042-1.703, P = 0.022). Furthermore, there were family-based associations for allele T of rs10877012 and allele T of rs4646536 in both vitamin D deficient families and obese families (P < 0.05). Both rs10877012 and rs4646536 were associated with serum 25(OH)D3 levels between siblings (P < 0.05), but not BMI (P > 0.05). In addition, there is linkage disequilibrium between rs10877012 and rs4646536 (D' = 1.0, r 2  = 0.992)., Conclusion: Vitamin D deficiency may be a causal factor of obesity. Maintaining sufficient vitamin D is beneficial to obesity prevention.