<i>TYK2</i> protein-coding variants identified by exon-sequencing of RA cases and controls.

<p>Using dense genotyping, we demonstrate that three <i>TYK2</i> protein-coding variants predicted to be damaging, P1104A, A928V, and I684S, protect against RA (highlighted in red). By exon-sequencing in 1,118 RA cases and 1,118 controls, we identified 23 additional missense variants predicted to be damaging (PolyPhen-2 and SIFT), with no strong evidence of association to RA in gene-based association tests. The <i>TYK2</i> coding exons, the protein domains, and the minor allele count (MAC) of the rare variants (MAC<5) in cases and controls are shown.