The imprinted DLK1-MEG3 gene region on chromosome 14q32.2 alters susceptibility to type 1 diabetes

Genomewide association studies to map common disease susceptibility loci have been hugely successful with over 300 reproducibly associated loci reported to date,1 but, perhaps surprisingly, have not yet provided convincing evidence for any susceptibility locus subject to parent of origin effects. We used imputation to extend existing genomewide association datasets2, 3, 4 and here report robust evidence, at rs941576, for paternally inherited risk of type 1 diabetes (T1D, ratio of allelic effects for paternal vs maternal transmissions = 0.75, 95%CI=0.71–0.79), in the imprinted region of chromosome 14q32.2, which contains a functional candidate gene, DLK1. Our meta-analysis also provided support at genomewide significance for a T1D locus at chromosome 19p13.2, with the highest association at marker rs2304256 (OR=0.86, 95%CI=0.82–0.90) in the TYK2 gene, which has previously associated with systemic lupus erythematosus.5