One study reported lower vagal tone, as measured by heart rate variability, in CD patients compared with healthy controls, and another report showed that patients with high resting vagal tone had lower circulating TNF.59,60 Furthermore, in patients with ulcerative colitis, an association was observed between higher parasympathetic activity during a flare of the disease and lower systemic inflammation during a 3-year follow-up.61 An association has also been reported between a history of vagotomy and the development of CD.58 The gene discussed is TNF; the disease is Cowden disease.