title: The genetic basis of quality of life in healthy Swedish women: a candidate gene approach.
abstract: BACKGROUND
  Quality of life (QoL) is an increasingly important parameter in clinical practice as it predicts mortality and poor health outcomes. It is hypothesized that one may have a genetic predisposition for QoL. We therefore related 139 candidate genes, selected through a literature search, to QoL in healthy females.
  
  
  METHODS
  In 5,142 healthy females, background characteristics (i.e. demographic, clinical, lifestyle, and psychological factors) were assessed. QoL was measured by the EORTC QLQ-C30, which consists of 15 domains. For all women genotype information was available. For each candidate gene, single nucleotide polymorphisms (SNPs) were identified based on their functional (n = 2,663) and physical annotation (n = 10,649). SNPs were related to each QoL-domain, while controlling for background characteristics and population stratification. Finally, gene-based analyses were performed relating the combined effect of 10,649 SNPs (selected based on physical annotation) for each gene, to QoL using the statistical software package VEGAS.
  
  
  RESULTS
  Overall, we found no relation between genetic variations (SNPs and genes) and 14 out of 15 QoL-domains. The strongest association was found between cognitive functioning and the top SNP rs1468951 (p = 1.21E-05) in the GSTZ1 gene. Furthermore, results of the gene-based test showed that the combined effect of 11 SNPs within the GSTZ1 gene is significantly associated with cognitive functioning (p = 2.60E-05).
  
  
  CONCLUSIONS
  If validated, the involvement of GSTZ1 in cognitive functioning underscores its heritability which is likely the result of differences in the dopamine pathway, as GSTZ1 contributes to the equilibrium between dopamine and its neurotoxic metabolites via the glutathione redox cycle.
authors: 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.
authors: Dounya
authors: D
authors: Schoormans
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Human Genetics, Genome Institute of Singapore, Singapore, Singapore.
authors: Jingmei
authors: J
authors: Li
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Hatef
authors: H
authors: Darabi
authors: Department of Oncology-Pathology, Karolinska Institutet, Stockholm, Sweden.
authors: Yvonne
authors: Y
authors: Brandberg
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden; Department of Medical Psychology, Academic Medical Center, Amsterdam, The Netherlands.
authors: Mirjam A G
authors: MA
authors: Sprangers
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Mikael
authors: M
authors: Eriksson
authors: Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, The Netherlands.
authors: Koos H
authors: KH
authors: Zwinderman
authors: Department of Medical Epidemiology and Biostatistics, Karolinska Institutet, Stockholm, Sweden.
authors: Per
authors: P
authors: Hall
mesh_terms: D000328:Adult; D000368:Aged; D000483:Alleles; D002874:Chromosome Mapping; D019295:Computational Biology; D005260:Female; D056726:Genetic Association Studies; D055106:Genome-Wide Association Study; D005838:Genotype; D006304:Health Status; D006801:Humans; D008019:Life Style; D008875:Middle Aged; D058977:Molecular Sequence Annotation; D020641:Polymorphism, Single Nucleotide; D062486:Public Health Surveillance; D011788:Quality of Life; D040641:Quantitative Trait Loci; D012307:Risk Factors; D013548:Sweden; D044465:White People / Q000235:genetics*; D016387:Women's Health