CORNET Saliva Cortisol GWAS Summary Statistics

Summary statistics for CORNET GWAS on <br>morning saliva cortisol levels. <br><br>Alexander Neumann, Nese Direk, Andrew A. Crawford, Saira Mirza, Hieab Adams, Jennifer Bolton, Caroline Hayward, David P. Strachan, Erin K. Payne, Jennifer A. Smith, Yuri Milaneschi, Brenda Penninx, Jouke J. Hottenga, Eco de Geus, Albertine J. Oldehinkel, Peter J. van der Most, Yolanda de Rijke, Brian R. Walker, Henning Tiemeier, <br>The low single nucleotide polymorphism heritability of plasma and saliva cortisol levels, <br>Psychoneuroendocrinology, <br>Volume 85, <br>2017, <br>Pages 88-95, <br>ISSN 0306-4530, <br>https://doi.org/10.1016/j.psyneuen.2017.08.011. <br>(https://www.sciencedirect.com/science/article/pii/S0306453017305826) <br>Abstract: Cortisol is an important stress hormone affected by a variety of biological and environmental factors, such as the circadian rhythm, exercise and psychological stress. Cortisol is mostly measured using blood or saliva samples. A number of genetic variants have been found to contribute to cortisol levels with these methods. While the effects of several specific single genetic variants is known, the joint genome-wide contribution to cortisol levels is unclear. Our aim was to estimate the amount of cortisol variance explained by common single nucleotide polymorphisms, i.e. the SNP heritability, using a variety of cortisol measures, cohorts and analysis approaches. We analyzed morning plasma (n=5705) and saliva levels (n=1717), as well as diurnal saliva levels (n=1541), in the Rotterdam Study using genomic restricted maximum likelihood estimation. Additionally, linkage disequilibrium score regression was fitted on the results of genome-wide association studies (GWAS) performed by the CORNET consortium on morning plasma cortisol (n=12,597) and saliva cortisol (n=7703). No significant SNP heritability was detected for any cortisol measure, sample or analysis approach. Point estimates ranged from 0% to 9%. Morning plasma cortisol in the CORNET cohorts, the sample with the most power, had a 6% [95%CI: 0–13%] SNP heritability. The results consistently suggest a low SNP heritability of these acute and short-term measures of cortisol. The low SNP heritability may reflect the substantial environmental and, in particular, situational component of these cortisol measures. Future GWAS will require very large sample sizes. Alternatively, more long-term cortisol measures such as hair cortisol samples are needed to discover further genetic pathways regulating cortisol concentrations.<br>针对晨间唾液皮质醇水平的CORNET全基因组关联研究（GWAS, Genome-Wide Association Study）汇总统计 作者：Alexander Neumann, Nese Direk, Andrew A. Crawford, Saira Mirza, Hieab Adams, Jennifer Bolton, Caroline Hayward, David P. Strachan, Erin K. Payne, Jennifer A. Smith, Yuri Milaneschi, Brenda Penninx, Jouke J. Hottenga, Eco de Geus, Albertine J. Oldehinkel, Peter J. van der Most, Yolanda de Rijke, Brian R. Walker, Henning Tiemeier 论文标题：《血浆与唾液皮质醇水平的单核苷酸多态性（SNP, Single Nucleotide Polymorphism）遗传力较低》 期刊：《Psychoneuroendocrinology》（《心理神经内分泌学》） 卷：85 发表年份：2017年 页码：88-95 国际标准刊号（ISSN）：0306-4530 DOI链接：https://doi.org/10.1016/j.psyneuen.2017.08.011 ScienceDirect原文链接：https://www.sciencedirect.com/science/article/pii/S0306453017305826 摘要：皮质醇是一种重要的应激激素，受昼夜节律、运动与心理应激等多种生物及环境因素影响。临床中皮质醇检测多采用血液或唾液样本，目前已发现多个遗传变异与皮质醇水平相关。尽管已知部分单基因变异对皮质醇水平的调控效应，但全基因组层面的联合遗传贡献仍不明确。本研究旨在通过多种皮质醇检测指标、队列及分析方案，评估常见单核苷酸多态性（SNP）对皮质醇水平变异的解释度，即SNP遗传力。我们采用基因组限制性最大似然估计法，对鹿特丹队列中的晨间血浆皮质醇（样本量n=5705）、唾液皮质醇（n=1717）及日间唾液皮质醇（n=1541）数据进行了分析。此外，本研究还针对CORNET联盟开展的晨间血浆皮质醇（n=12597）与唾液皮质醇（n=7703）全基因组关联研究（GWAS）结果，采用连锁不平衡得分回归进行拟合分析。结果显示，所有皮质醇检测指标、样本类型及分析方法均未检测到显著的SNP遗传力，点估计值区间为0%~9%。其中检验效能最高的CORNET队列晨间血浆皮质醇样本，其SNP遗传力点估计为6%[95%置信区间（CI, Confidence Interval）：0%~13%]。本研究结果一致表明，这类急性短期皮质醇检测指标的SNP遗传力较低。该现象或反映了此类皮质醇指标受较强的环境因素，尤其是情境因素影响。未来的GWAS研究需采用更大的样本量，或可通过毛发皮质醇等长期皮质醇检测指标，进一步挖掘调控皮质醇浓度的遗传通路。