title: Biological pathways, candidate genes, and molecular markers associated with quality-of-life domains: an update.
abstract: BACKGROUND
  There is compelling evidence of a genetic foundation of patient-reported quality of life (QOL). Given the rapid development of substantial scientific advances in this area of research, the current paper updates and extends reviews published in 2010.
  
  
  OBJECTIVE
  The objective was to provide an updated overview of the biological pathways, candidate genes, and molecular markers involved in fatigue, pain, negative (depressed mood) and positive (well-being/happiness) emotional functioning, social functioning, and overall QOL.
  
  
  METHODS
  We followed a purposeful search algorithm of existing literature to capture empirical papers investigating the relationship between biological pathways and molecular markers and the identified QOL domains.
  
  
  RESULTS
  Multiple major pathways are involved in each QOL domain. The inflammatory pathway has the strongest evidence as a controlling mechanism underlying fatigue. Inflammation and neurotransmission are key processes involved in pain perception, and the catechol-O-methyltransferase (COMT) gene is associated with multiple sorts of pain. The neurotransmitter and neuroplasticity theories have the strongest evidence for their relationship with depression. Oxytocin-related genes and genes involved in the serotonergic and dopaminergic pathways play a role in social functioning. Inflammatory pathways, via cytokines, also play an important role in overall QOL.
  
  
  CONCLUSIONS
  Whereas the current findings need future experiments and replication efforts, they will provide researchers supportive background information when embarking on studies relating candidate genes and/or molecular markers to QOL domains. The ultimate goal of this area of research is to enhance patients' QOL.
authors.affiliation: Department of Medical Psychology/J3-211, Academic Medical Center, University of Amsterdam, Meibergdreef 15, 1105 AZ, Amsterdam, The Netherlands, m.a.sprangers@amc.uva.nl.
authors.forename: Mirjam A G
authors.initials: MA
authors.lastname: Sprangers
authors.forename: Melissa S Y
authors.initials: MS
authors.lastname: Thong
authors.forename: Meike
authors.initials: M
authors.lastname: Bartels
authors.forename: Andrea
authors.initials: A
authors.lastname: Barsevick
authors.forename: Juan
authors.initials: J
authors.lastname: Ordoñana
authors.forename: Qiuling
authors.initials: Q
authors.lastname: Shi
authors.forename: Xin Shelley
authors.initials: XS
authors.lastname: Wang
authors.forename: Pål
authors.initials: P
authors.lastname: Klepstad
authors.forename: Eddy A
authors.initials: EA
authors.lastname: Wierenga
authors.forename: Jasvinder A
authors.initials: JA
authors.lastname: Singh
authors.forename: Jeff A
authors.initials: JA
authors.lastname: Sloan
mesh_terms: D000339:Affect / Q000502:physiology*; D015415:Biomarkers / Q000378:metabolism; D003863:Depression / Q000235:genetics* / Q000378:metabolism; D005221:Fatigue / Q000235:genetics* / Q000378:metabolism; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease / Q000235:genetics / Q000523:psychology*; D006240:Happiness; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000523:psychology; D010146:Pain / Q000235:genetics* / Q000523:psychology; D011788:Quality of Life
chemical_list: D015415:Biomarkers; D005819:Genetic Markers