GSTM1 and obesity due to melanocortin 4 receptor deficiency: Tsuji et al. (1996) suggested that a 1-SD reduction in overall HRV was associated with a relative risk of 1.47 for cardiac events over 3.5 years of follow-up. Although differences in study design preclude a quantitative risk estimate, the observed reduction in overall HRV in subjects with SHS exposure (>2 hr) and either obesity, GSTM1 deletion, or GSTP1 substitution in our study suggests a nontrivial elevation of cardiovascular risk on follow-up, and one similar to what has in fact been reported for SHS exposure (Law and Wald 2003).