Fig. 1: Multiomics approach to identify sequence variants that associate with autoimmune thyroid disease (AITD) and point to candidate causal genes.
a A GWAS meta-analysis on 110,945 cases and 1,084,290 controls from Iceland, Finland, UK and USA was performed to identify sequence variants that associate with AITD. For lead signals, a systematic variant annotation was applied, identifying AITD lead variants or correlated variants (r2 > 0.8) that affect protein coding (Supplementary Data 1 and 3), mRNA expression (top cis-eQTL or sQTL, Supplementary Data 4–6) or levels of proteins in plasma (top cis-pQTL, Supplementary Data 1 and Supplementary Data 7–8). b Out of 280 AITD lead variants outside the MHC-region, 141 sequence variants point to candidate genes, of which 25 variants pointing to 26 genes increased the risk of AITD by ≥10%, as shown in the figure, ranked by effect size (odds ratio, OR), calculated using logistic regression analysis assuming a multiplicative model, with two-sided P-values adjusted for year of birth, sex and origin (Iceland) or the first principal components (UK, USA), and Bonferroni adjustments for multiple comparisons, see details in Methods. In addition, the variant at the HLA locus with largest effect is shown. All effects are shown for the AITD risk increasing allele based on meta-analysis of study populations from Iceland, Finland, UK and USA. Previously unreported associations (GWAS catalog with P < 5 × 10−8) with AITD or related phenotypes (Graves’ disease, Hashimoto’s thyroiditis, hypo- or hyperthyroidism) are marked with *.
