Of note, we found eight loci significantly associated with abnormal TSH levels (PDE8B, PDE10, CAPZB, VEGFA, NR3C2, FGF7, NFIA and ITPK1), of which two were specifically associated with either abnormally low (VEGFA) or elevated (NR3C2) TSH values, suggesting differential mechanisms for the contribution of these variants to hyper- and hypothyroidism, respectively. This evidence concerns the gene PDE8B and hypothyroidism.