CYP27B1 as an instrument gene to investigate the causal relationship between vitamin D deficiency and obesity: a family-based study

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. 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  0.05). In addition, there is linkage disequilibrium between rs10877012 and rs4646536 (D′ = 1.0, r2 = 0.992). Vitamin D deficiency may be a causal factor of obesity. Maintaining sufficient vitamin D is beneficial to obesity prevention. Vitamin D deficiency was associated with obesity. But their causal relationship is still controversial. CYP27B1 plays a direct role in circulating the concentration of 25(OH)D, which can be used to investigate causal relationships. In this study, allele T of rs10877012 and allele T of rs4646536 in CYP27B1 were family-based linked with both vitamin D deficiency and obesity. In addition, both rs10877012 and rs4646536 were associated with serum 25(OH)D3 levels between siblings but not BMI. Therefore, vitamin D deficiency may be a causal factor of obesity. Maintaining sufficient vitamin D is beneficial to obesity prevention.