Unaffected Individuals Cases CDKN2A N Mean# Range (Min-Max) P P* N Mean# Range (Min-Max) P P* All Non-Carrier 262 132 33-2644     77 111 36-1588     All Carrier 40 162 52-1604 0.080 0.20 59 144 45-1022 0.024 0.01 ROS-RelatedCarrier 30 174 52-781 0.038 0.16 36 141 48-713 0.035 0.04

Table 3: Mean mtDNA copy number by CDKN2A mutation status. P-values were obtained by comparing CDKN2A mutation carriers and non-carriers by CMM status using linear regression analysis of natural log-transformed data adjusting for familial correlation in the variance using a generalized estimating equation approach (P) with further adjustment for age at blood draw and sex (P*). Using box-cox transformed (λ=-0.75) data did not alter the results significantly. # Geometric means (or exponentiation of log-transformed mtDNA copy number).