A Bidirectional Mendelian Randomization Study to evaluate the causal role of reduced blood vitamin D levels with type 2 diabetes risk in South Asians and Europeans.
A Bidirectional Mendelian Randomization Study to evaluate the causal role of reduced blood vitamin D levels with type 2 diabetes risk in South Asians and Europeans.
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DOI：
10.1186/s12937-021-00725-1
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发表时间：
2021-07-27
影响因子：
5.4
通讯作者：
Sanghera DK
中科院分区：
文献类型：
--
作者：
Bejar CA;Goyal S;Afzal S;Mangino M;Zhou A;van der Most PJ;Bao Y;Gupta V;Smart MC;Walia GK;Verweij N;Power C;Prabhakaran D;Singh JR;Mehra NK;Wander GS;Ralhan S;Kinra S;Kumari M;de Borst MH;Hyppönen E;Spector TD;Nordestgaard BG;Blackett PR;Sanghera DK
多项观察性研究报告了25-羟基维生素D浓度(25(OH)D)与2型糖尿病(T2D)之间的负相关关系。然而，关于25(OH)D和T2D风险之间的关系的短期和长期干预试验的结果并不一致。为了评估低血25(OH)D在T2D中的因果作用，我们对来自欧洲和亚洲印度血统的59,890名个体(5,862名T2D患者和54,028名对照)进行了双向孟德尔随机研究。我们使用了6个已知的SNPs，包括3个T2D SNPs和3个维生素D途径SNPs，作为遗传学工具来评估T2D和循环25(OH)D浓度之间的因果关系和方向。8项研究的联合Meta分析结果显示，3个T2D SNP的综合得分将显著增加T2D风险，其优势比(OR)为1.2 4，p = 为1.82 × 10-32；Z得分为11.86，但与25(OH)D状态无关(β-0.02nmol/L ± SE 0.01nmol/L；p = 0.83；Z得分-0.21)。同样，25(OH)D降低等位基因的综合评分显著降低25(OH)D浓度(-2.1nmol/L ± SE 0.1nmol/L，p = 7.92 × 10-78；Z评分-18.68)，但与T2D风险增加无关(OR1.00，p = 0.12；Z评分1.54)。然而，使用25(OH)D合成SNP(DHR7；rs12785878)作为个体遗传工具，预测每个等位基因25(OH)D浓度降低(-4.2nmol/L ± SE 0.3nmol/L)将增加5%的T2D风险，p = 0.004；Z值2.84。然而，当作为单独的仪器使用时，这种效应在其他25(OH)D SNP(GC rs2282679，CYP2R1 rs12794714)中没有看到。我们关于这项双向孟德尔随机化研究的新数据表明，遗传工具控制的T2D风险不会导致25(OH)D水平的变化。然而，由维生素D合成基因(DHCR7)引起的基因调控的25(OH)D缺乏可能影响T2D的风险。网上版载有补充材料，可在10.1186/s12937-021-00725-1查阅。
Multiple observational studies have reported an inverse relationship between 25-hydroxyvitamin D concentrations (25(OH)D) and type 2 diabetes (T2D). However, the results of short- and long-term interventional trials concerning the relationship between 25(OH)D and T2D risk have been inconsistent. To evaluate the causal role of reduced blood 25(OH)D in T2D, here we have performed a bidirectional Mendelian randomization study using 59,890 individuals (5,862 T2D cases and 54,028 controls) from European and Asian Indian ancestries. We used six known SNPs, including three T2D SNPs and three vitamin D pathway SNPs, as a genetic instrument to evaluate the causality and direction of the association between T2D and circulating 25(OH)D concentration. Results of the combined meta-analysis of eight participating studies showed that a composite score of three T2D SNPs would significantly increase T2D risk by an odds ratio (OR) of 1.24, p = 1.82 × 10–32; Z score 11.86, which, however, had no significant association with 25(OH)D status (Beta -0.02nmol/L ± SE 0.01nmol/L; p = 0.83; Z score -0.21). Likewise, the genetically instrumented composite score of 25(OH)D lowering alleles significantly decreased 25(OH)D concentrations (-2.1nmol/L ± SE 0.1nmol/L, p = 7.92 × 10–78; Z score -18.68) but was not associated with increased risk for T2D (OR 1.00, p = 0.12; Z score 1.54). However, using 25(OH)D synthesis SNP (DHCR7; rs12785878) as an individual genetic instrument, a per allele reduction of 25(OH)D concentration (-4.2nmol/L ± SE 0.3nmol/L) was predicted to increase T2D risk by 5%, p = 0.004; Z score 2.84. This effect, however, was not seen in other 25(OH)D SNPs (GC rs2282679, CYP2R1 rs12794714) when used as an individual instrument. Our new data on this bidirectional Mendelian randomization study suggests that genetically instrumented T2D risk does not cause changes in 25(OH)D levels. However, genetically regulated 25(OH)D deficiency due to vitamin D synthesis gene (DHCR7) may influence the risk of T2D. The online version contains supplementary material available at 10.1186/s12937-021-00725-1.
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影响因子：
5.1
作者：
Guariguata, L.;Whiting, D. R.;Shaw, J. E.
通讯作者：
Shaw, J. E.
DOI：
10.1016/j.jsbmb.2010.06.013
发表时间：
2010-10
影响因子：
4.1
作者：
Engelman, Corinne D.;Meyers, Kristin J.;Ziegler, Julie T.;Taylor, Kent D.;Palmer, Nicholette D.;Haffner, Steven M.;Fingerlin, Tasha E.;Wagenknecht, Lynne E.;Rotter, Jerome I.;Bowden, Donald W.;Langefeld, Carl D.;Norris, Jill M.
通讯作者：
Norris, Jill M.
影响因子：
7.7
作者：
Saxena R;Saleheen D;Been LF;Garavito ML;Braun T;Bjonnes A;Young R;Ho WK;Rasheed A;Frossard P;Sim X;Hassanali N;Radha V;Chidambaram M;Liju S;Rees SD;Ng DP;Wong TY;Yamauchi T;Hara K;Tanaka Y;Hirose H;McCarthy MI;Morris AP;DIAGRAM;MuTHER;AGEN;Basit A;Barnett AH;Katulanda P;Matthews D;Mohan V;Wander GS;Singh JR;Mehra NK;Ralhan S;Kamboh MI;Mulvihill JJ;Maegawa H;Tobe K;Maeda S;Cho YS;Tai ES;Kelly MA;Chambers JC;Kooner JS;Kadowaki T;Deloukas P;Rader DJ;Danesh J;Sanghera DK
通讯作者：
Sanghera DK
影响因子：
5.8
作者：
Johnson, Andrew D.;Handsaker, Robert E.;de Bakker, Paul I. W.
通讯作者：
de Bakker, Paul I. W.
影响因子：
16.2
作者：
Scragg, R;Sowers, M;Bell, C
通讯作者：
Bell, C