COMT and irritable bowel syndrome: In COMT rs4680 gene dosage models of change in IBS-SSS from baseline to 6 weeks, increasing the number of met alleles was associated with a greater reduction in IBS symptom severity (beta (SE), −22.3 (10.0), p = 0.027) such that participants homozygous for the low activity met allele (met/met) had the greatest placebo response across all participants in the three treatment arms combined (Figure 1B).