m.9899T>C (MT-CO3) was identified as a common mtDNA variant interacted with CRP in male subjects with self-reported anxiety (P value = 6.00 × 10−3), all subjects with GAD score(P value = 9.95 × 10−4), and all subjects with PHQ-9 score (P value = 2.15 × 10−6), male subjects with PHQ-9 score (P value = 2.03 × 10−4), female subjects with PHQ-9 score (P value = 1.61 × 10−3). Here, CRP is linked to generalized anxiety disorder.