Evaluation of Genetic Markers as Instruments for Mendelian Randomization Studies on Vitamin D
Evaluation of Genetic Markers as Instruments for Mendelian Randomization Studies on Vitamin D
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DOI：
10.1371/journal.pone.0037465
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发表时间：
2012-05-21
期刊：
影响因子：
3.7
通讯作者：
Hyppoenen, Elina
中科院分区：
文献类型：
--
作者：
Berry, Diane J.;Vimaleswaran, Karani S.;Hyppoenen, Elina
背景：孟德尔随机化 (MR) 研究使用模仿可修改暴露影响的遗传变异来评估和量化与结果的因果关系，目的是避免影响其他类型观察性研究的混杂和反向因果关系问题。目的：我们评估了指示 25-羟基维生素 D (25(OH) D) 差异的遗传标记，作为维生素 D MR 研究的工具。方法和结果：我们使用了来自1958 年英国出生队列中的 6,877 名参与者拥有遗传标记和 25(OH) D 信息。作为潜在工具，我们选择了位于维生素 D 代谢途径或影响皮肤色素沉着/晒黑的 20 个单核苷酸多态性 (SNP)，其中包括来自 25(OH) D 全基因组关联 (GWA) 荟萃分析的 4 个 SNP。我们分析了 SNP 与 25(OH) D 的关联并评估了等位基因的使用将基因分为影响 25(OH)D 合成（DHCR7、CYP2R1）和代谢（GC、CYP24A1、CYP27B1）的基因。除了 GWA SNP 之外，只有两个 SNP（CYP27B1、OCA2）显示出与 25(OH)D 相关的证据，并且在生活方式调整后 OCA2 关联被消除。每个等位基因差异在 -0.02 和 -0.08 nmol/L 之间变化（P
Background: Mendelian randomization (MR) studies use genetic variants mimicking the influence of a modifiable exposure to assess and quantify a causal association with an outcome, with an aim to avoid problems with confounding and reverse causality affecting other types of observational studies.Aim: We evaluated genetic markers that index differences in 25-hydroxyvitamin D (25(OH) D) as instruments for MR studies on vitamin D.Methods and Findings: We used data from up-to 6,877 participants in the 1958 British birth cohort with information on genetic markers and 25(OH) D. As potential instruments, we selected 20 single nucleotide polymorphisms (SNP) which are located in the vitamin D metabolism pathway or affect skin pigmentation/tanning, including 4 SNPs from genome-wide association (GWA) meta-analyses on 25(OH) D. We analyzed SNP associations with 25(OH) D and evaluated the use of allele scores dividing genes to those affecting 25(OH) D synthesis (DHCR7, CYP2R1) and metabolism (GC, CYP24A1, CYP27B1). In addition to the GWA SNPs, only two SNPs (CYP27B1, OCA2) showed evidence for association with 25(OH) D, with the OCA2 association abolished after lifestyle adjustment. Per allele differences varied between -0.02 and -0.08 nmol/L (P