Rothwell S, et al. - Given that among patients with idiopathic inflammatory myopathies (IIM), the strongest genetic risk is within the major histocompatibility complex [MHC, also known as the human leucocyte antigen (HLA) region] and that autoantibody presence defines specific clinical subgroups of IIM, researchers sought to identify novel risk variants in the MHC region that co-occur with IIM autoantibodies via correlating serotype and genotype. They analyzed the autoantibody data in the cohort of 2582 Caucasian patients with IIM and identified for the first time genetic differences between adult-onset and juvenile-onset patients with anti-TIF1 autoantibodies. This indicates distinct aetiologies and disease mechanisms in adult and juvenile onset disease with the same autoantibody. For the development of anti-Jo-1 autoantibodies, they identified independent associations of HLA-DRB1 and HLA-B, implicating multiple genetic features of the 8.1 ancestral haplotype. They identified novel associations with autoantibodies with amino acid imputation; these associations were noted as stronger than classical HLA associations, indicating key positions within HLA molecules that may confer risk.