Genetically low vitamin D concentrations and increased mortality: Mendelian randomisation analysis in three large cohorts.
Genetically low vitamin D concentrations and increased mortality: Mendelian randomisation analysis in three large cohorts.
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DOI：
10.1136/bmj.g6330
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发表时间：
2014-11-18
期刊：
影响因子：
--
通讯作者：
Nordestgaard BG
中科院分区：
文献类型：
--
作者：
Afzal S;Brøndum-Jacobsen P;Bojesen SE;Nordestgaard BG
目的验证遗传低的25-羟基维生素D浓度与死亡率增加相关的假设。设计孟德尔随机化分析。背景：哥本哈根城市心脏研究、哥本哈根普通人群研究和哥本哈根缺血性心脏病研究。参与者来自三个队列的95 766名丹麦裔白人参与者，中位随访时间分别为19.1年、5.8年和7.9年，对影响血浆25-羟基维生素D浓度的DHCR7和CYP2R1基因变异进行了基因分型；35334人也进行了血浆25-羟基维生素D测量。参与者从研究开始一直跟踪到2013年，在此期间有10349人死亡。主要结果衡量所有原因死亡率和特定原因死亡率，根据世界卫生组织的全球健康状况，对所有原因死亡率的共同风险因素进行调整。结果血浆25-羟基维生素D浓度低于20nmol/L的多变量调整风险比为：全因死亡1.19(95%可信区间1.14~1.25)，心血管死亡1.18(1.09~1.28)，癌症死亡1.12(1.03~1.22)，其他死亡1.27(1.15~1.40)。等位基因得分每增加一次，血浆25-羟基维生素D浓度降低1.9nmol/L，全因、癌症和其他死亡率增加，但与心血管疾病死亡率无关。基因决定的血浆25-羟基维生素D浓度降低20nmol/L对全因死亡率的优势比为1.3(1.05比1.61)，相应的观察性多变量调整后的优势比为1.21(1.11比1.31)。相应的遗传和观察优势比心血管疾病死亡率为0.77(0.55~1.08)和1.13(1.03~1.24)，癌症死亡率为1.43(1.02~1.99)和1.10(1.02~1.19)，其他死亡率为1.44(1.01~2.04)和1.17(1.06~1.29)。在敏感性分析中，结果是稳健的。结论：遗传低的25-羟基维生素D浓度与全因死亡率、癌症死亡率和其他死亡率的增加有关，但与心血管死亡率的增加无关。这些发现与这样一种观点是一致的，即遗传上较低的25-羟基维生素D浓度可能与癌症和其他死亡率有因果关系，但也表明，观察到的与心血管死亡率的关联可能是混淆的结果。
Objective To test the hypothesis that genetically low 25-hydroxyvitamin D concentrations are associated with increased mortality. Design Mendelian randomisation analysis. Setting Copenhagen City Heart Study, Copenhagen General Population Study, and Copenhagen Ischemic Heart Disease Study. Participants 95 766 white participants of Danish descent from three cohorts, with median follow-up times of 19.1, 5.8, and 7.9 years, genotyped for genetic variants in DHCR7 and CYP2R1 affecting plasma 25-hydroxyvitamin D concentrations; 35 334 also had plasma 25-hydroxyvitamin D measurements. Participants were followed from study entry through 2013, during which time 10 349 died. Main outcome measures All cause mortality and cause specific mortality, adjusted for common risk factors for all cause mortality based on the World Health Organization’s global health status. Results The multivariable adjusted hazard ratios for a 20 nmol/L lower plasma 25-hydroxyvitamin D concentration were 1.19 (95% confidence interval 1.14 to 1.25) for all cause mortality, 1.18 (1.09 to 1.28) for cardiovascular mortality, 1.12 (1.03 to 1.22) for cancer mortality, and 1.27 (1.15 to 1.40) for other mortality. Each increase in DHCR7/CYP2R1 allele score was associated with a 1.9 nmol/L lower plasma 25-hydroxyvitamin D concentration and with increased all cause, cancer, and other mortality but not with cardiovascular mortality. The odds ratio for a genetically determined 20 nmol/L lower plasma 25-hydroxyvitamin D concentration was 1.30 (1.05 to 1.61) for all cause mortality, with a corresponding observational multivariable adjusted odds ratio of 1.21 (1.11 to 1.31). Corresponding genetic and observational odds ratios were 0.77 (0.55 to 1.08) and 1.13 (1.03 to 1.24) for cardiovascular mortality, 1.43 (1.02 to 1.99) and 1.10 (1.02 to 1.19) for cancer mortality, and 1.44 (1.01 to 2.04) and 1.17 (1.06 to 1.29) for other mortality. The results were robust in sensitivity analyses. Conclusions Genetically low 25-hydroxyvitamin D concentrations were associated with increased all cause mortality, cancer mortality, and other mortality but not with increased cardiovascular mortality. These findings are compatible with the notion that genetically low 25-hydroxyvitamin D concentrations may be causally associated with cancer and other mortality but also suggest that the observational association with cardiovascular mortality could be the result of confounding.
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影响因子：
3.5
作者：
Ahn J;Yu K;Stolzenberg-Solomon R;Simon KC;McCullough ML;Gallicchio L;Jacobs EJ;Ascherio A;Helzlsouer K;Jacobs KB;Li Q;Weinstein SJ;Purdue M;Virtamo J;Horst R;Wheeler W;Chanock S;Hunter DJ;Hayes RB;Kraft P;Albanes D
通讯作者：
Albanes D
影响因子：
2.2
作者：
Manson JE;Bassuk SS;Lee IM;Cook NR;Albert MA;Gordon D;Zaharris E;Macfadyen JG;Danielson E;Lin J;Zhang SM;Buring JE
通讯作者：
Buring JE
影响因子：
7.7
作者：
Brion, Marie-Jo A.;Shakhbazov, Konstantin;Visscher, Peter M.
通讯作者：
Visscher, Peter M.
影响因子：
5.8
作者：
Haase, Christiane L.;Tybjaerg-Hansen, Anne;Frikke-Schmidt, Ruth
通讯作者：
Frikke-Schmidt, Ruth
影响因子：
3.7
作者：
Berry, Diane J.;Vimaleswaran, Karani S.;Hyppoenen, Elina
通讯作者：
Hyppoenen, Elina