(A) The goal of genetic fine mapping is to progress from multiple linked SNPs to one (or very few) candidate causal SNPs. Bayesian algorithms have been developed to fine map credible sets of candidate causal SNPs (37, 86) on the basis of dense genotyping data (e.g., Immunochip data [ref. 76]) or on the basis of imputation of sparser genotyping data to the 1000 Genomes Project (87). (B) Approximately 90% of causal variants associated with autoimmune diseases are noncoding. Genome-wide chromatin maps of active regulatory elements in primary immune cells in both resting and stimulated conditions serve as a powerful resource to identify functional noncoding elements that can be disrupted by disease-associated variants. Candidate causal disease variants (red box) map to regulatory elements (notably enhancers) active in specialized cell types, especially stimulated CD4⁺ T cell subsets. Enhancers contain binding sites for transcription factors and regulate transcription through long-range interactions with RNA polymerase (RNA Pol) machinery (88). The locations of disease-associated SNPs highlight pathogenic cell types and cell conditions based on the activity patterns of affected enhancers. Quantitative trait studies are beginning to characterize the functional effects of causal autoimmune disease variants in modulating transcription factor (TF) binding (circles), chromatin state, target gene regulation, and cellular phenotype. Detailed studies might eventually diagnose specific gene regulatory defects caused by autoimmune disease variants and provide novel targets for therapeutic intervention. Adapted with permission from Immunity (116).