最近精读的文献题目为：Association between circulating 25-hydroxyvitamin D and incident type 2 diabetes: a mendelian randomisation study
1. Summary
- Who: Zheng Ye, Stephen J Sharp
- How: We did a mendelian randomisaition and analysis using SNPs within or near four genes related to 25(OH)D synthesis and metabolism, then compared it with that from a meta-analysis of data from observational studies that assessed the association between 25(OH)D concentration and type 2 diabetes.
- What: The mendelian randomisation-derived unconfounded odds ratio for type 2 diabetes per 1 SD lower 25(OH)D concentration was not significant. The corresponding relative risk from the meta-analysis of data from observational studies was significant.
- Why: Whether the association between 25(OH)D and type 2 diabetes is causal remains unclear.
2. Elegant and concise descriptions
- Efforts to increase 25(OH)D concentrations might not reduce the risk of type 2 diabetes as would be expected on the basis of observational evidence.
- Studies of genetic variants (single nucleotide polymorphisms, SNPs) that specifically affect 25(OH)D concentration can provide another route to draw causal inference.
- We only included studies in which participants were of European descent for comparability with our mendelian randomisation analysis.
- Among adults without diabetes in prospective and case-control studies, we examined whether each SNP as an instrumental variable fulfilled the assumption of mendelian randomisation analysis that a SNP has no association with potential confounders.
- We examined associations of each SNP with risk of type 2 diabetes, assuming a linear effect of each SNP on the logit of disease risk (in logistic models) or on the linear predictor of disease risk (in the Cox model) per additional variant allele.
- This limitation could be minimised by examining several SNPs from a single gene or from the whole genome as polygenic effects, although increasing the diversity of the SNP panel also brings increased potential for pleiotropic effects.
3. Pros and cons
Pros: The contrast of results of mendelian randomisaition and observational studies
Cons: Introducing bias due to different study designs, be limited to elucidate a causal role of biologically active vitamin D, four SNPs account for only 3·6% of the variation in 25(OH)D concentration, hard to distinguish between endogenous 25(OH)D3 and exogenous vitamin D, the lack of generalizability
4. New knowledge
- learning about the mendelian randomisaition
