Schoormans Dounya, Darabi Hatef, Li Jingmei, Brandberg Yvonne, Eriksson Mikael, Zwinderman Koos H, Sprangers Mirjam A G, Hall Per
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Medical Psychology, Academic Medical Center, Amsterdam, The Netherlands; Department of Medical and Clinical Psychology, Tilburg University, Tilburg, The Netherlands.
Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
PLoS One. 2015 Oct 15;10(10):e0140563. doi: 10.1371/journal.pone.0140563. eCollection 2015.
Quality of life (QoL) is increasingly measured in both research and clinical practice. QoL-assessments are built on a long, empirically-based, and stringent approach. There is ample evidence that QoL is, in part, heritable. We therefore performed a GWAS relating genetic variation to QoL in healthy females.
In 5,142 healthy females, background characteristics (e.g. demographic, clinical, lifestyle and psychological factors) and QoL by means of the EORTC QLQ-C30 were measured. Moreover, women were genotyped using a custom array including ~210,000 single nucleotide polymorphisms (SNPs). Initially, SNPs were related to each QoL-domain, by means of partially adjusted (controlling for age and population stratification) and fully adjusted (controlling for age, population stratification, and background characteristics) regression analyses. Additionally, gene-based analyses were performed relating the combined effect of SNPs within each gene to QoL using the statistical software package VEGAS.
None of the associations between QoL and genetic variation (i.e. individual SNPs and genes) reached the bonferroni corrected significance level.
Reasons for a lack of association between genetic markers and QoL could be low variation in QoL-scores; selecting genetic markers not tagging QoL; or that the genetic effect that impacts one's QoL is mediated through biological pathways rather than the effect of single SNPs or genes. Therefore, we opt for a pathway-based or system biology approach as a complementary and powerful approach to analyze the combined effect of genes and their biological implications in future studies focusing on QoL-issues.
生活质量（QoL）在研究和临床实践中越来越多地得到衡量。生活质量评估建立在长期、基于经验且严格的方法之上。有充分证据表明生活质量在一定程度上是可遗传的。因此，我们对健康女性进行了一项全基因组关联研究（GWAS），将基因变异与生活质量相关联。
在5142名健康女性中，测量了背景特征（如人口统计学、临床、生活方式和心理因素）以及通过欧洲癌症研究与治疗组织生活质量问卷核心30项（EORTC QLQ-C30）得出的生活质量。此外，使用包含约210,000个单核苷酸多态性（SNP）的定制阵列对女性进行基因分型。最初，通过部分调整（控制年龄和群体分层）和完全调整（控制年龄、群体分层和背景特征）回归分析，将SNP与每个生活质量领域相关联。此外，使用统计软件包VEGAS进行基于基因的分析，将每个基因内SNP的综合效应与生活质量相关联。
生活质量与基因变异（即单个SNP和基因）之间的关联均未达到Bonferroni校正的显著性水平。
基因标记与生活质量缺乏关联的原因可能是生活质量评分变异低；选择未标记生活质量的基因标记；或者影响一个人生活质量的基因效应是通过生物学途径介导的，而不是单个SNP或基因的效应。因此，我们选择基于途径或系统生物学方法作为一种补充性且强大的方法，以在未来关注生活质量问题的研究中分析基因的综合效应及其生物学意义。
