Creating and Validating a DNA Methylation-Based Proxy for Interleukin-6.
Creating and Validating a DNA Methylation-Based Proxy for Interleukin-6.
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DOI：
10.1093/gerona/glab046
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发表时间：
2021-11-15
期刊：
影响因子：
--
通讯作者：
Marioni RE
中科院分区：
文献类型：
--
作者：
Stevenson AJ;Gadd DA;Hillary RF;McCartney DL;Campbell A;Walker RM;Evans KL;Harris SE;Spires-Jones TL;McRae AF;Visscher PM;McIntosh AM;Deary IJ;Marioni RE
评估慢性炎症和认知功能之间关系的研究产生了不同的结果。一个潜在的原因是炎症介质的可变性，这可能导致对个体持续炎症水平的错误分类。DNA甲基化（DNAm）在索引环境暴露方面显示出实用性，并可用于提供慢性炎症的代理签名。我们对875名老年人（Lothian出生队列1936;平均年龄：70岁）进行了白细胞介素-6（IL-6）的弹性净回归，以开发基于DNAm的预测因子。在一个独立的队列中对预测因子进行了检验（苏格兰一代; N = 7028 [417例测量了IL-6]，平均年龄：51岁）。35个CpG位点的加权评分在独立测试集中最佳预测了IL-6（苏格兰一代; R2 = 4.4%，p = 2.1 × 10−5）。在独立的测试队列中，测量的IL-6和DNAm替代物均随年龄增加（血清IL-6：n = 417，β = 0.02，SE = 0.004，p = 1.3 × 10−7; DNAm IL-6评分：N = 7028，β = 0.02，SE = 0.0009，p < 2 × 10−16）。血清IL-6与认知能力无关（n = 417，β = −0.06，SE = 0.05，p = 0.19）;然而，DNA m评分与认知功能之间存在负相关（N = 7028，β = −0.16，SE = 0.02，pFDR < 2 × 10−16）。这些结果表明，基于甲基化的预测因子可用作炎症标志物的替代物，可能有助于进一步了解炎症与相关健康结果之间的关系。
Studies evaluating the relationship between chronic inflammation and cognitive functioning have produced heterogeneous results. A potential reason for this is the variability of inflammatory mediators which could lead to misclassifications of individuals’ persisting levels of inflammation. DNA methylation (DNAm) has shown utility in indexing environmental exposures and could be leveraged to provide proxy signatures of chronic inflammation. We conducted an elastic net regression of interleukin-6 (IL-6) in a cohort of 875 older adults (Lothian Birth Cohort 1936; mean age: 70 years) to develop a DNAm-based predictor. The predictor was tested in an independent cohort (Generation Scotland; N = 7028 [417 with measured IL-6], mean age: 51 years). A weighted score from 35 CpG sites optimally predicted IL-6 in the independent test set (Generation Scotland; R2 = 4.4%, p = 2.1 × 10−5). In the independent test cohort, both measured IL-6 and the DNAm proxy increased with age (serum IL-6: n = 417, β = 0.02, SE = 0.004, p = 1.3 × 10−7; DNAm IL-6 score: N = 7028, β = 0.02, SE = 0.0009, p < 2 × 10−16). Serum IL-6 did not associate with cognitive ability (n = 417, β = −0.06, SE = 0.05, p = .19); however, an inverse association was identified between the DNAm score and cognitive functioning (N = 7028, β = −0.16, SE = 0.02, pFDR < 2 × 10−16). These results suggest methylation-based predictors can be used as proxies for inflammatory markers, potentially allowing for further insight into the relationship between inflammation and pertinent health outcomes.
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影响因子：
4.6
作者：
Chatziioannou A;Georgiadis P;Hebels DG;Liampa I;Valavanis I;Bergdahl IA;Johansson A;Palli D;Chadeau-Hyam M;Siskos AP;Keun H;Botsivali M;de Kok TM;Pérez AE;Kleinjans JC;Vineis P;Kyrtopoulos SA;EnviroGenomarkers project consortium
通讯作者：
EnviroGenomarkers project consortium
DOI：
10.5114/ceji.2015.54603
发表时间：
2015
期刊：
Central-European journal of immunology
影响因子：
--
作者：
Conti P;Shaik-Dasthagirisaeb Y
通讯作者：
Shaik-Dasthagirisaeb Y
影响因子：
4.1
作者：
Deary IJ;Gow AJ;Taylor MD;Corley J;Brett C;Wilson V;Campbell H;Whalley LJ;Visscher PM;Porteous DJ;Starr JM
通讯作者：
Starr JM
影响因子：
12.3
作者：
Ligthart S;Marzi C;Aslibekyan S;Mendelson MM;Conneely KN;Tanaka T;Colicino E;Waite LL;Joehanes R;Guan W;Brody JA;Elks C;Marioni R;Jhun MA;Agha G;Bressler J;Ward-Caviness CK;Chen BH;Huan T;Bakulski K;Salfati EL;WHI-EMPC Investigators;Fiorito G;CHARGE epigenetics of Coronary Heart Disease;Wahl S;Schramm K;Sha J;Hernandez DG;Just AC;Smith JA;Sotoodehnia N;Pilling LC;Pankow JS;Tsao PS;Liu C;Zhao W;Guarrera S;Michopoulos VJ;Smith AK;Peters MJ;Melzer D;Vokonas P;Fornage M;Prokisch H;Bis JC;Chu AY;Herder C;Grallert H;Yao C;Shah S;McRae AF;Lin H;Horvath S;Fallin D;Hofman A;Wareham NJ;Wiggins KL;Feinberg AP;Starr JM;Visscher PM;Murabito JM;Kardia SL;Absher DM;Binder EB;Singleton AB;Bandinelli S;Peters A;Waldenberger M;Matullo G;Schwartz JD;Demerath EW;Uitterlinden AG;van Meurs JB;Franco OH;Chen YI;Levy D;Turner ST;Deary IJ;Ressler KJ;Dupuis J;Ferrucci L;Ong KK;Assimes TL;Boerwinkle E;Koenig W;Arnett DK;Baccarelli AA;Benjamin EJ;Dehghan A
通讯作者：
Dehghan A
影响因子：
3.8
作者：
González-Quintela, A;Dominguez-Santalla, MJ;Barrio, E
通讯作者：
Barrio, E