| Description: |
Normal thyroid function is essential for health, but its genetic architecture remains poorly understood. Here, for the heritable thyroid traits thyrotropin (TSH) and free ?thyroxine (FT4), we analyse whole-genome sequence data from the UK10K project (N=2,287). Using additional whole-genome sequence and deeply imputed data sets, we report meta-analysis results for common variants (MAF=1%) associated with TSH and FT4 (N=16,335). For TSH, we identify a novel variant in ?SYN2 (MAF=23.5%, P=6.15 × 10-9) and a new independent variant in ?PDE8B (MAF=10.4%, P=5.94 × 10-14). For FT4, we report a low-frequency variant near ?B4GALT6/?SLC25A52 (MAF=3.2%, P=1.27 × 10-9) tagging a rare ?TTR variant (MAF=0.4%, P=2.14 × 10-11). All common variants explain =20% of the variance in TSH and FT4. Analysis of rare variants (MAF |