Supplementary Materials

Supplementary Material for:

Resolving TYK2 locus genotype-to-phenotype differences in autoimmunity

Calliope A. Dendrou, Adrian Cortes, Lydia Shipman, Hayley G. Evans, Kathrine E. Attfield, Luke Jostins, Thomas Barber, Gurman Kaur, Subita Balaram Kuttikkatte, Oliver A. Leach, Christiane Desel, Soren L. Faergeman, Jane Cheeseman, Matt J. Neville, Stephen Sawcer, Alastair Compston, Adam R. Johnson, Christine Everett, John I. Bell, Fredrik Karpe, Mark Ultsch, Charles Eigenbrot, Gil McVean, Lars Fugger*

*Corresponding author. Email: lars.fugger{at}

Published 2 November 2016, Sci. Transl. Med. 8, 363ra149 (2016)
DOI: 10.1126/scitranslmed.aag1974

This PDF file includes:

  • Fig. S1. CRISPR-Cas9–modified HEK293T cell lines and their respective TYK2 expression and phosphorylation.
  • Fig. S2. CRISPR-Cas9–modified TYK2 knockout cell lines, their respective TYK2 expression, and impact of genetic modification on cytokine signaling.
  • Fig. S3. Summary data for Oxford BioBank blood donor cohort and representative optimization data for cytokine stimulation.
  • Fig. S4. Representative cytokine-induced pSTAT and IFN-β–induced pSTAT1 by the rs34536443 genotype in human primary immune cells.
  • Fig. S5. Downstream consequences of the rs34536443 genotype–dependent differential cytokine signaling.
  • Fig. S6. Signal 3 haplotype colocalization with epigenetic marks.
  • Fig. S7. Characterization of Tyk2 Ala1124 mice.
  • Fig. S8. Tyk2 P1124A mouse weight change and incidence after immunization, and draining lymph node cell cytokine production after restimulation with MOG peptide.
  • Fig. S9. Cytokine production after MOG peptide restimulation of CNS CD4+ T cells and clinical profile of Tyk2 Pro/Ala1124 mice after immunization.
  • Fig. S10. Immune profile of Oxford BioBank donor pairs by the rs34536443 genotype.
  • Fig. S11. Cytokine receptor expression by the rs34536443 genotype.
  • Fig. S12. Alignment of human TYK2 and JAK2 kinase domains and statistics for JAK2 (P1057A)/TG101209 structure.
  • Table S1. Summary of previously reported genetic associations in the TYK2 region.
  • Table S2. TYK2 region 90% credible sets for the three independent association signals identified by multinomial association analysis.
  • Table S3. TYK2 region associations for each of the autoimmune diseases included in the multinomial association analysis.
  • Table S4. Summary of TYK2 transcript expression by rs34536443 and rs9797854 genotypes across immune cell types.
  • Table S5. Evidence for nonadditivity of rs34536443 effect on pSTAT.
  • Table S6. Analysis of normalized pSTAT mean fluorescence intensity by the rs34536443 genotype.
  • Table S7. Analysis of frequency of pSTAT-positive primary human immune cells by the rs12720356 genotype.
  • Table S8. Analysis of normalized pSTAT mean fluorescence intensity in primary human immune cells by the rs12720356 genotype.
  • Table S9. Summary of eQTL colocalizations with TYK2 region association signal 3.
  • Table S10. Association of the rs34536443 genotype with U.K. Biobank health record phenotypes.
  • Table S11. Relationship between genotype-dependent cytokine signaling and risk for autoimmune disease and certain recurrent or severe infections.

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