To determine whether loneliness-related increases in NF-κB/GRE ratios might stem from correlated differences in other demographic, medical, psychological, social, or behavioral characteristics, additional ANCOVAs adjusted gene expression profiles for those characteristics prior to bioinformatic analysis of transcription control pathways. NF-κB/GRE ratios remained significantly elevated in high-lonely individuals following control for demographic factors (including age, gender, race, marital status, and household income; all p ≤ 0.0249), other established psychological risk factors for disease (including depression, perceived stress, and hostility; all p ≤ 0.0334), medical conditions (including hypertension, coronary artery disease, myocardial infarct, emphysema, rheumatoid arthritis, cancer, ulcers, and strokes or other neurological disorders; all p ≤ 0.0395), other biomedical parameters (including body mass index and use of statins, beta-blockers, anti-inflammatory agents, diuretics, antidepressants, and other psychiatric medications; all p ≤ 0.0486), and behavioral risk factors (including smoking and alcohol consumption; all p ≤ 0.0085). Socially isolated individuals showed a nonsignificant trend toward greater diagnosed diabetes and use of anti-diabetic agents, but elevated NF-κB/GRE ratios continued to approach statistical significance despite control for those factors (both p ≤ 0.0594).