The relationship between SSc risk and C4A and C4B gene CNs exhibited consistent, logical patterns across the 18 different CN combinations of C4A and C4B (Fig. 1a, b), which is based on an interaction between C4A and C4B CNs that was suggested by logistic-regression analysis (bc4a:c4b = −0.14, P = 2.1 × 10−5). Here, C4B is linked to systemic sclerosis.