The scientists found that, compared with controls, individuals with CFS have different levels of expression of genes with roles in the hypothalamic-pituitary-adrenal axis and the sympathetic nervous system—specifically, genes involved in how the body responds to hormones and other chemical messengers that are released in response to challenges and stressors such as trauma, injury, and other adverse events. In addition, the investigators identified 28 out of several million possible single nucleotide polymorphisms (common variations of DNA sequences found throughout the genome) that predicted with 76% accuracy whether an individual had CFS. The 3 genes containing the most relevant and frequent of these polymorphisms are associated with brain function, stress reactions, and emotional responses. Genetic tests based on these findings might help drug developers design medications that target specific aspects of the syndrome as well as help physicians identify patients most likely to benefit from them. Other analyses revealed that study participants with CFS were approximately twice as likely as those without the syndrome to have a high allostatic load index (a measure of hormone secretions, blood pressure, and other signs of wear and tear on the body resulting from environmental stresses), findings that suggest that difficulty managing stress may be linked to the development of CFS. The scientists also found that individuals with CFS can be categorized into several subtypes based on criteria that take into account genetic profiles and symptoms (such as stress and fatigue levels). Despite these advances, much uncertainty still remains about CFS. The investigators were not able to identify definitive genetic markers of CFS or determine how each genetic variation influences the symptoms. More work remains to define how genetic profiles might be used to diagnose CFS, a condition that is currently diagnosed by symptom duration and pattern and the exclusion of other known medical conditions. Reeves noted that he and his collaborators are currently trying to replicate the findings of these studies with data gathered from 30 000 people representative of the metropolitan, urban, and rural populations of Georgia.