In stage I, two SNPs (rs7530810 and rs1321108) in the 5' flanking region of the TSHB gene demonstrated significant synergistic interactions with one tagging intronic SNP (rs13172105) in the ADAMTS16 gene (odds ratios, 6.63 and 5.57; 95% CIs, 2.30-19.18 and 2.05-15.12; P = 0.00048 and 0.00074, respectively) although the SNPs were not significantly associated with POF in a single SNP model.