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Genome-wide association (GWA) studies to map common disease susceptibility loci have been hugely successful, with over 300 reproducibly associated loci reported to date. However, these studies have not yet provided convincing evidence for any susceptibility locus subject to parent-of-origin effects. Using imputation to extend existing GWA datasets, we have obtained robust evidence at rs941576 for paternally inherited risk of type 1 diabetes (T1D; ratio of allelic effects for paternal versus maternal transmissions = 0.75; 95% confidence interval (CI) = 0.71-0.79). This marker is in the imprinted region of chromosome 14q32.2, which contains the functional candidate gene DLK1. Our meta-analysis also provided support at genome-wide significance for a T1D locus at chromosome 19p13.2. The highest association was at marker rs2304256 (odds ratio (OR) = 0.86; 95%CI = 0.82-0.90) in the TYK2 gene, which has previously been associated with systemic lupus erythematosus and multiple sclerosis.

Original publication




Journal article


Nat Genet

Publication Date





68 - 71


Calcium-Binding Proteins, Chromosomes, Human, Pair 14, Diabetes Mellitus, Type 1, Family Health, Female, Genetic Predisposition to Disease, Genome-Wide Association Study, Genomic Imprinting, Genotype, Humans, Intercellular Signaling Peptides and Proteins, Linkage Disequilibrium, Male, Membrane Proteins, Meta-Analysis as Topic, Polymorphism, Single Nucleotide, Proteins, RNA, Long Noncoding